npj Regenerative Medicine最新文献

Priming of human iPSCs with doxorubicin causes genome-wide transcriptional reprogramming and functional impairments in iPSC-derived cardiomyocytes. 用阿霉素引发人ipsc导致ipsc衍生心肌细胞全基因组转录重编程和功能损伤。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-10-10 DOI: 10.1038/s41536-026-00513-7

Michelle Westerhoff, Roohallah Ghodrat, Nahal Brocke-Ahmadinejad, Yulia Schaumkessel, Karl Köhrer, Arif Dönmez, Timo Dellmann, David Pla-Martín, Christian Henninger, Andrea Borchardt, Lluís Enjuanes-Ruiz, Julia Tigges, Katharina Koch, Gerhard Fritz, Arun Kumar Kondadi, Andreas S Reichert

{"title":"Priming of human iPSCs with doxorubicin causes genome-wide transcriptional reprogramming and functional impairments in iPSC-derived cardiomyocytes.","authors":"Michelle Westerhoff, Roohallah Ghodrat, Nahal Brocke-Ahmadinejad, Yulia Schaumkessel, Karl Köhrer, Arif Dönmez, Timo Dellmann, David Pla-Martín, Christian Henninger, Andrea Borchardt, Lluís Enjuanes-Ruiz, Julia Tigges, Katharina Koch, Gerhard Fritz, Arun Kumar Kondadi, Andreas S Reichert","doi":"10.1038/s41536-026-00513-7","DOIUrl":"https://doi.org/10.1038/s41536-026-00513-7","url":null,"abstract":"How Doxorubicin (Dox) mediated damage to stem cells or cardiomyocytes contributes to cardiotoxicity and cardiac regeneration is unclear. Using a human iPSC-based model together with corresponding iPSC-derived cardiomyocytes (iCMs) revealed that iPSCs are much more sensitive against single short pulse-treatments with Dox than iCMs. Major mitochondrial impairments such as increased mitochondrial fragmentation, loss of mitochondrial membrane potential, reduced ATP levels, and altered mitochondrial DNA (mtDNA) organization, yet neither increased ROS formation, nuclear DNA damage response, nor apoptosis were detected in Dox-treated iPSCs. Whole genome transcriptome profiling revealed major differences in the transcriptional response to Dox including downregulation of genes regulating cellular homeostasis and energy metabolism. Dox exposure at the iPSC stage, termed priming here, shifts the global transcriptional landscape of iCMs towards reduced cardiac muscle regeneration, energy metabolism, muscle contraction, and increased fibrosis. Functionally, priming caused iCMs to 'memorize' this early Dox treatment resulting in reduced ATP levels, altered mtDNA organization, and in impaired contractility and oscillating Ca2+ handling. We propose that Dox-induced mitochondrial dysfunction and transcriptional priming in stem cells alters durably cardiac and bioenergetic properties of its progeny which may impair the regenerative capacity after differentiation. This may be of particular relevance for children and teenagers undergoing chemotherapy.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skeletal muscle dedifferentiation requires centrosomes. 骨骼肌去分化需要中心体。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-09-25 DOI: 10.1038/s41536-026-00509-3

Elaiyaraja Subramanian, Anoop Kumar, Ketan Mishra, Gonçalo Brito, Matthew Kirkham, András Simon

{"title":"Skeletal muscle dedifferentiation requires centrosomes.","authors":"Elaiyaraja Subramanian, Anoop Kumar, Ketan Mishra, Gonçalo Brito, Matthew Kirkham, András Simon","doi":"10.1038/s41536-026-00509-3","DOIUrl":"10.1038/s41536-026-00509-3","url":null,"abstract":"Multinucleated skeletal muscle cells are stably withdrawn from the cell cycle in most vertebrates. Muscle dedifferentiation, however, naturally occurs during limb regeneration in newts and can be experimentally induced in mammalian myotubes. Here we addressed the dynamics of centrosomes, which are key organelles for cell proliferation during myogenic differentiation and dedifferentiation in a cross-species comparative setting. We show that, unlike their mammalian counterparts, newt muscle cells retain centrosomes during differentiation, and their abrogation during regeneration interferes with myogenic dedifferentiation as well as blastema formation in newts. Mammalian myotubes, which are experimentally induced to dedifferentiate, give rise to progeny that regain centrosomes through a process that depends on inhibition of the tumor suppressor, p53. We also find that regulation of the subcellular localization of Polo-Like Kinase 4, rather than its expression level, is a hallmark of myogenic differentiation and dedifferentiation, revealing a novel cellular process underlying the plasticity of the differentiated state.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13612385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic-delivering endotracheal tubes heal intubation injury via mucosal remodeling and disrupting the inflammation-microbiome-fibrosis triad. 输送治疗性气管内管通过粘膜重塑和破坏炎症-微生物组-纤维化三联体来治愈插管损伤。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-21 DOI: 10.1038/s41536-026-00497-4

Gabriela Gonzales, Ronit Malka, Solaleh Miar, Joo L Ong, Rena Bizios, Gregory R Dion, Teja Guda

{"title":"Therapeutic-delivering endotracheal tubes heal intubation injury via mucosal remodeling and disrupting the inflammation-microbiome-fibrosis triad.","authors":"Gabriela Gonzales, Ronit Malka, Solaleh Miar, Joo L Ong, Rena Bizios, Gregory R Dion, Teja Guda","doi":"10.1038/s41536-026-00497-4","DOIUrl":"https://doi.org/10.1038/s41536-026-00497-4","url":null,"abstract":"Endotracheal intubation is essential in clinical care but often exacerbates airway inflammation, fibrosis, and microbial dysbiosis, contributing to long-term complications. This study investigates how newly developed, coated endotracheal tubes (ETTs) modulate airway healing through localized therapeutic delivery in a swine model of laryngotracheal injury. Animals were intubated with uncoated, dexamethasone-coated, or composite-coated (dexamethasone + PEG hydrogel delivering siRNA against smad3) ETTs for 3, 7, or 14 days. Tissues were analyzed via mechanical testing, immunohistochemistry, ELISA, cytokine profiling, 16S rRNA sequencing, and microscopy. Therapeutic coatings induced region- and time-dependent alterations in airway stiffness and extracellular matrix composition, including remodeling of collagen IV, laminin, and elastin. Reduced nuclear pSMAD3 staining in composite-treated airways relative to uninjured controls provided supportive, indirect evidence of altered SMAD3 pathway activity following smad3-targeting siRNA delivery, although downstream TGF-β1 and collagen I expression did not significantly differ across treatment groups or over the time course. Composite-coated ETTs also promoted a temporal shift from pro-inflammatory (M1) toward reparative (M2) macrophage phenotypes and altered local cytokine profiles. Microbial community composition varied by coating type and duration, with treatment-associated changes in bacterial taxa and predicted metabolic pathways. Mucin composition also shifted over time, reflecting evolving epithelial responses during prolonged intubation. These findings demonstrate that localized therapeutic delivery influences interconnected mechanical, inflammatory, and microbial responses during airway healing and supports the development of multifunctional ETT coatings as a strategy to modulate post-intubation airway remodeling.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

HGF mRNA LNP therapy promotes uterine repair after cesarean section in a mouse model. HGF mRNA LNP治疗促进小鼠剖宫产术后子宫修复。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-21 DOI: 10.1038/s41536-026-00494-7

Xue-Ning Li, Wei-Jing Kong, Jia-Xin Li, Xiao-Nan Xu, Yu-Jia Zhai, Wen Gu, Wei Chen, Tian-Chen Wu, Juan Du, Zhuo-Fan Fang, Peng-Bo Yuan, Kai Wang, Li-Ying Yan, Yuan Wei

{"title":"HGF mRNA LNP therapy promotes uterine repair after cesarean section in a mouse model.","authors":"Xue-Ning Li, Wei-Jing Kong, Jia-Xin Li, Xiao-Nan Xu, Yu-Jia Zhai, Wen Gu, Wei Chen, Tian-Chen Wu, Juan Du, Zhuo-Fan Fang, Peng-Bo Yuan, Kai Wang, Li-Ying Yan, Yuan Wei","doi":"10.1038/s41536-026-00494-7","DOIUrl":"https://doi.org/10.1038/s41536-026-00494-7","url":null,"abstract":"Previous cesarean scar defect (PCSD) is the most common complication following cesarean delivery, characterized by myometrial thinning or disruption. Its incidence rises with increasing number of cesarean sections, reaching 76% after three procedures, yet effective clinical interventions remain lacking. Inadequate blood supply and weak regeneration of the lower uterine segment are key pathogenic contributors, suggesting that improving local perfusion could facilitate wound healing. In this study, we developed lipid nanoparticle (LNP)-encapsulated hepatocyte growth factor (HGF) mRNA and applied it locally to uterine incisions in a mouse model. HGF mRNA LNP treatment significantly increased endometrial thickness and gland density, reduced collagen deposition, and promoted smooth muscle regeneration and angiogenesis at days 7 and 30 postoperatively. Favorable trends in pregnancy outcomes were observed. Hematological and serum biochemical parameters remained comparable between groups at all time points examined. Transcriptomic profiling revealed that upregulated genes in the HGF mRNA LNP group were involved in cell proliferation, migration, and survival. In vitro, HGF enhanced endothelial cell migration and tube formation. Collectively, these findings indicate that HGF mRNA LNP delivery at the site of uterine incision injury can promote structural and functional uterine repair in a small‑animal model, and provide a rationale for further preclinical evaluation.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148551437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prophylactic inhibition of LATS1/2 before high-dose irradiation promotes the regeneration of the damaged intestinal epithelium. 高剂量辐照前预防性抑制LATS1/2可促进受损肠上皮的再生。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-20 DOI: 10.1038/s41536-026-00496-5

Lucy M Driver, Frances Anne Tosto, Bridget S Scherer, Lixia Luo, Katy Harbaugh, Olivia White, Ayra Charania, Jordan Tran, Rebecca Bacon, Patrick J Morris, Michele Ceribelli, Damien Y Duveau, Lale Evsen, Scott B Hoyt, Keerthana Kurapati, Koravit Poysungnoen, John W Hickey, Jatin Roper, Christine E Eyler, Craig J Thomas, Chang-Lung Lee

{"title":"Prophylactic inhibition of LATS1/2 before high-dose irradiation promotes the regeneration of the damaged intestinal epithelium.","authors":"Lucy M Driver, Frances Anne Tosto, Bridget S Scherer, Lixia Luo, Katy Harbaugh, Olivia White, Ayra Charania, Jordan Tran, Rebecca Bacon, Patrick J Morris, Michele Ceribelli, Damien Y Duveau, Lale Evsen, Scott B Hoyt, Keerthana Kurapati, Koravit Poysungnoen, John W Hickey, Jatin Roper, Christine E Eyler, Craig J Thomas, Chang-Lung Lee","doi":"10.1038/s41536-026-00496-5","DOIUrl":"10.1038/s41536-026-00496-5","url":null,"abstract":"Following radiation injury, intestinal epithelial cells adapt through cellular plasticity to regenerate and repopulate the damaged epithelium by activating Yap, a key effector protein of the Hippo signaling pathway. However, the impact of pharmacologically targeting the Hippo pathway on the regeneration of the irradiated intestinal epithelium remains poorly understood. Here, we investigated this question using NCGC-023, a selective and potent small-molecule inhibitor of Yap's upstream regulators LATS1/2. NCGC-023 treatment significantly increased active Yap protein expression in human enteroids and protected them against ionizing radiation (IR) in vitro. In mice, transient treatment with NCGC-023 before IR reduced radiation-induced DNA damage, suppressed premitotic apoptosis and aberrant mitosis in intestinal crypt cells, facilitated regenerative reprogramming of the damaged intestinal epithelium, and improved survival of mice subjected to IR doses that precipitate gastrointestinal acute radiation syndrome (GI-ARS). Mechanistically, NCGC-023 treatment before IR upregulated key signaling pathways controlled by LATS1/2, including Yap-dependent regenerative responses involving Il-33 and Yap-independent cellular responses to heavy metals mediated by metallothioneins. Moreover, NCGC-023 treatment did not exacerbate delayed injury in multiple organs of mice that survived 4 months post-irradiation. Together, these results demonstrate that transient NCGC-023 treatment before high-dose IR promotes the regeneration of the damaged intestinal epithelium. This proof-of-concept study supports further development of LATS1/2 inhibitors as prophylactic medical countermeasures for GI-ARS.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gli2-serpinh1 drives fibroblast state transition during skin wound healing. Gli2-serpinh1在皮肤伤口愈合过程中驱动成纤维细胞状态转变。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-14 DOI: 10.1038/s41536-026-00483-w

Rui Ma, Wang Wu, Chuqing Zhou, Zeming Li, Jiajun Tan, Jingwei Jiang, Yiping Zhao, Mengyue Wang, Yuanli Ye, Siyi Zhou, Xudong Qiu, Fanbin Meng, Xiao Xiang, Mingxing Lei

{"title":"Gli2-serpinh1 drives fibroblast state transition during skin wound healing.","authors":"Rui Ma, Wang Wu, Chuqing Zhou, Zeming Li, Jiajun Tan, Jingwei Jiang, Yiping Zhao, Mengyue Wang, Yuanli Ye, Siyi Zhou, Xudong Qiu, Fanbin Meng, Xiao Xiang, Mingxing Lei","doi":"10.1038/s41536-026-00483-w","DOIUrl":"https://doi.org/10.1038/s41536-026-00483-w","url":null,"abstract":"Dermal fibroblasts exhibit spatiotemporal heterogeneity, transitioning from coordinating immune signaling and depositing a provisional extracellular matrix during the early inflammatory phase to driving directional migration and mature matrix synthesis in the proliferative phase of wound healing. However, the molecular mechanisms underlying these fibroblast state transitions remain unclear. Here, by integrating single-cell RNA-sequencing, spatial transcriptomics, and in vivo and in vitro analyses in both mouse and skin organoid models for functional validation, we identify a previously underappreciated Gli2-Serpinh1 regulatory axis that plays a key role in fibroblast state transitions during skin wound healing. Serpinh1⁺ fibroblast subsets drive wound closure through re-epithelialization, vascular regeneration, and actin-mediated filopodia formation. Gli2, as a key upstream regulator of Serpinh1, modulates fibroblast function in a level-dependent manner across different healing states. Leveraging organoid technology as a drug discovery platform, we further identify three traditional Chinese medicine candidates that enhance wound healing by activating the Gli2-Serpinh1 axis. Our study reveals the Gli2-Serpinih1 axis as a pivotal regulator of fibroblast state transitions, providing mechanistic insight into fibroblast heterogeneity during wound healing and opening new avenues for precision regenerative therapies.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tie2-enriched nucleus pulposus cell transplantation enables severity-independent disc repair in a canine model with induced and controlled disc degeneration severity. 在具有诱导和控制的椎间盘退变严重程度的犬模型中，富铁髓核细胞移植能够实现与严重程度无关的椎间盘修复。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-10 DOI: 10.1038/s41536-026-00491-w

Jordy Schol, Takayuki Warita, Erika Matsushita, Takano Susumu, Asami Kawachi, Shota Tamagawa, Shota Ogasawara, Takafumi Konishi, Masato Sato, Masahiko Watanabe, Daisuke Sakai

{"title":"Tie2-enriched nucleus pulposus cell transplantation enables severity-independent disc repair in a canine model with induced and controlled disc degeneration severity.","authors":"Jordy Schol, Takayuki Warita, Erika Matsushita, Takano Susumu, Asami Kawachi, Shota Tamagawa, Shota Ogasawara, Takafumi Konishi, Masato Sato, Masahiko Watanabe, Daisuke Sakai","doi":"10.1038/s41536-026-00491-w","DOIUrl":"https://doi.org/10.1038/s41536-026-00491-w","url":null,"abstract":"Intervertebral disc (IVD) degeneration is characterized by extracellular matrix loss, impaired nucleus pulposus cell (NPC) function, and depletion of Tie2-positive NP progenitor cells, leading to progressive structural failure and potential pain. Although cell-based therapies are promising, their regenerative efficacy across different degeneration severities remains unclear. This study aims to assess whether Tie2-enriched NPC transplantation can induce structural regeneration independent of baseline degeneration severity. Human Tie2-enriched NPC products were formulated as an off-the-shelf (OTS) product in hyaluronic acid. Two canine models of induced IVD degeneration were used. In Part 1, degeneration was induced by NP aspiration, followed by saline or OTS cell injection. In Part 2, dogs were randomized to mild or severe degeneration, with severe degeneration including additional surgical punch extraction. Outcomes included radiographic disc height index (DHI), MRI over a 3-month follow-up period, as well as macroscopic and histological assessments and immunohistochemical evaluation of human cell persistence. OTS-NPC transplantation significantly improved DHI and histological scores compared to sham treatment in both study parts. Regenerative effects were observed in both mild and severe degeneration models, resulting in comparable structural outcomes. In short, Tie2-enriched OTS-NPC demonstrated regenerative efficacy across degeneration severities in a clinically relevant animal model, supporting further translational development.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148426481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lumican deficiency dysregulates trophoblast function via PI3K/AKT and P53 signaling in preeclampsia. Lumican缺乏症在子痫前期通过PI3K/AKT和P53信号通路失调滋养细胞功能。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-07 DOI: 10.1038/s41536-026-00493-8

Xin Wang, Qi Zhang, Yi Ren, Kunzheng Fan, Chao Liu, Huijie Gao

{"title":"Lumican deficiency dysregulates trophoblast function via PI3K/AKT and P53 signaling in preeclampsia.","authors":"Xin Wang, Qi Zhang, Yi Ren, Kunzheng Fan, Chao Liu, Huijie Gao","doi":"10.1038/s41536-026-00493-8","DOIUrl":"https://doi.org/10.1038/s41536-026-00493-8","url":null,"abstract":"Lumican, an extracellular matrix (ECM) component highly expressed in placenta, is implicated in preeclampsia (PE) pathogenesis, though its precise mechanisms in trophoblast function and PE development remain unclear. Transcriptomic analysis of a PE rat model induced by L-NAME revealed altered placental gene expression. Lumican expression progressively increased throughout rat and human gestation but was significantly downregulated in PE patient and model placentas. Functional assays showed shRNA-mediated lumican knockdown inhibited trophoblast proliferation, migration, and invasion while promoting apoptosis. This knockdown also influenced the phosphorylation of key proteins within the PI3K/AKT and P53 signaling pathways. Co-treatment with the PI3K agonist 740 Y-P activated this pathway, enhancing trophoblast proliferation and invasion, effects antagonized by lumican knockdown. In vivo, adenovirus-mediated lumican shRNA induced PE-like phenotypes: elevated systolic blood pressure, increased 24 h urinary protein, higher plasma sFlt-1 levels and sFlt-1/PlGF ratio. Histopathological analyses demonstrated abnormal placental villi development and renal glomerular endothelial damage. Immunohistochemistry confirmed lumican deficiency reduced PI3K, AKT, and MDM2 while upregulating P53 in placental tissues. Collectively, our findings demonstrate that reduced lumican expression contributes to PE by impairing trophoblast function via disruption of the PI3K/AKT and P53 signaling pathway, thus providing a mechanistic basis for its further exploration as a diagnostic marker and therapeutic target.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148406821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair. tgf - α /EGFR信号介导维甲酸诱导的肺修复。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-04 DOI: 10.1038/s41536-026-00492-9

Sek-Shir Cheong, Chunyu Yan, Róisín Mongey, David Chambers, Mark Griffiths, Matthew Hind, Charlotte H Dean

{"title":"TGF-alpha/EGFR signalling mediates retinoic acid-induced lung repair.","authors":"Sek-Shir Cheong, Chunyu Yan, Róisín Mongey, David Chambers, Mark Griffiths, Matthew Hind, Charlotte H Dean","doi":"10.1038/s41536-026-00492-9","DOIUrl":"https://doi.org/10.1038/s41536-026-00492-9","url":null,"abstract":"Lung repair involves coordination of multicellular processes, including endothelial angiogenesis and epithelial repopulation. Retinoic acid (RA) signalling is crucial for lung development, homeostasis, and repair; however, the mechanisms through which RA drives repair are still unknown. It has previously been shown that RA has no direct effects on the repair of alveolar epithelium, yet in animal studies, RA induces alveolar regeneration. Here we show that RA induces endothelial angiogenesis, which is associated with enhanced paracrine signalling to alveolar epithelial cells. Transcriptomic profiling of RA-treated HPMECs undergoing angiogenesis revealed enrichment of wound healing pathways, and subsequent in silico analysis identified several candidate mediators of endothelial-epithelium crosstalk. Scratch assays demonstrated that of these candidates, only TGFα promoted wound healing in alveolar epithelial A549 and primary human alveolar type 2 (hAT2) cells. Mechanistically, TGFα was associated with increased epithelial cell migration and activation of EGFR signalling, without detectable effects on proliferation or apoptosis. Our findings indicate that RA-induced endothelial angiogenesis promotes epithelial EGFR signalling through paracrine mediators, including TGFα. This study highlights the importance of endothelial-epithelial interactions in lung repair and provides insight into pathways that may be targeted to enhance alveolar regeneration.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":" ","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148388130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy. 多组学分析揭示了通过抗衰老治疗使衰老肾脏系统性年轻化。

IF 7 1区医学

npj Regenerative Medicine Pub Date : 2026-07-01 DOI: 10.1038/s41536-026-00490-x

Shilin Chen, Chenglin Zhang, Pengxu Cang, Weiming Guo, Liang Xiao, Yaohui He, Qiang Su, Shuhui Ouyang, Jinhui Zha, Gulikezi Maimaitirexiati, Yuling Chen, Xiaoyan Qi, Shiheng He, Qingping Zhang, Yao Xu, Jing Yang, Gang Fan

{"title":"Multi-omics profiling reveals systemic rejuvenation of the aged kidney through senolytic therapy.","authors":"Shilin Chen, Chenglin Zhang, Pengxu Cang, Weiming Guo, Liang Xiao, Yaohui He, Qiang Su, Shuhui Ouyang, Jinhui Zha, Gulikezi Maimaitirexiati, Yuling Chen, Xiaoyan Qi, Shiheng He, Qingping Zhang, Yao Xu, Jing Yang, Gang Fan","doi":"10.1038/s41536-026-00490-x","DOIUrl":"10.1038/s41536-026-00490-x","url":null,"abstract":"Cellular senescence is a key driver of kidney aging, leading to functional decline and increased susceptibility to chronic kidney disease. While the senolytic combination of dasatinib and quercetin (D + Q) has shown promise in mitigating age-related pathologies, its long-term effects and underlying multi-level systemic mechanisms in the aging kidney remain poorly defined. Here, we systematically evaluated the long-term effects of D + Q in naturally aged mice using multi-omics approaches. We show that D + Q treatment reduces senescence markers (p16, p21, SA-β-gal), restores the anti-aging protein Klotho, and attenuates renal fibrosis and inflammation. Proteomic profiling reveals that D + Q enhances apoptotic clearance of senescent cells and promotes proliferative and regenerative pathways. Moreover, D + Q reactivates PPARα signaling, improves fatty acid oxidation, and reduces lipid accumulation in aged kidneys. Single-cell transcriptomics further demonstrates that D + Q reverses transcriptional aging signatures across multiple renal cell types and remodels cell-type-specific pathways associated with metabolism, inflammation, and fibrosis. Cell-cell communication analysis reveals that D + Q normalizes the hyperconnected intercellular network in aged kidneys, particularly by modulating inflammation-related signaling. Our findings offer a comprehensive, systems-level understanding of how senolytic therapy restores renal homeostasis, emphasizing its potential as a multifaceted intervention to combat kidney aging.","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"11 1","pages":""},"PeriodicalIF":7.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0