Translational Research最新文献_第9页

Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells 免疫检查点活动通过增强肾小管上皮细胞中 PD-L1 的表达，加剧肾间质纤维化的进展。

IF 7.8 2区医学

Translational Research Pub Date : 2024-05-08 DOI: 10.1016/j.trsl.2024.05.004

Yuting Zhang , Xue Mi , Yunchao Zhang , Jipeng Li , Yunlong Qin , Peng He , Ya Zhao , Binxiao Su , Lijie He

{"title":"Immune checkpoint activity exacerbate renal interstitial fibrosis progression by enhancing PD-L1 expression in renal tubular epithelial cells","authors":"Yuting Zhang , Xue Mi , Yunchao Zhang , Jipeng Li , Yunlong Qin , Peng He , Ya Zhao , Binxiao Su , Lijie He","doi":"10.1016/j.trsl.2024.05.004","DOIUrl":"10.1016/j.trsl.2024.05.004","url":null,"abstract":"<div><p>Renal interstitial fibrosis (RIF) is often associated with inflammatory cell infiltration and no effective therapy. Programmed death cell-1 (PD-1) and its ligand PD-L1 were playing critical roles in T cell coinhibition and exhaustion, but the role in RIF is unclear. Here the data analyses of serum from 122 IgA nephrology (IgAN) patients showed that high level of soluble PD-1(sPD-1) was an independent risk factor for RIF and renal function progression. PD-L1 was also overexpressed in renal interstitial tissues from both IgAN patients with high level of sPD-1 and the unilateral ureteral obstruction (UUO) mouse. PD-L1 was significantly overexpressed in HK-2 cells with upregulated collagen and α-SMA when stimulated by inflammation or hypoxia in vitro. Additionally, matrix metalloproteinases (MMP-2) could increase the level of sPD-1 in culture supernatant when added in co-culture system of HK-2 and jurkat cells, which implied serum sPD-1 of IgAN might be cleaved by MMP-2 from T cells infiltrated into the tubulointerstitial inflammatory microenvironment. Crucially, injection of PD-L1 fusion protein, the blocker of sPD-1, could ameliorate kidney fibrosis in UUO mice by increasing T cell coinhibition and exhaustion, suggesting the therapeutic potential of PD-L1 fusion targeting for renal fibrosis. Take together, it reveals a novel causal role of sPD-1 in serum and PD-L1 of renal interstitial tissues in the development of renal fibrosis of IgAN, and targeting sPD-1 in serum by PD-L1 fusion protein is a potential therapeutic approach to prevent renal fibrosis of IgAN.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 52-67"},"PeriodicalIF":7.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000951/pdfft?md5=3edab8408ba1a3f8c26668d2e4f47c24&pid=1-s2.0-S1931524424000951-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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Information for Readers 读者信息

IF 7.8 2区医学

Translational Research Pub Date : 2024-05-06 DOI: 10.1016/S1931-5244(24)00088-4

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Editorial Advisory Board 编辑顾问委员会

IF 7.8 2区医学

Translational Research Pub Date : 2024-05-06 DOI: 10.1016/S1931-5244(24)00086-0

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Author Guidelines 作者指南

IF 7.8 2区医学

Translational Research Pub Date : 2024-05-06 DOI: 10.1016/S1931-5244(24)00087-2

引用次数: 0

Early growth response protein 2 promotes partial epithelial-mesenchymal transition by phosphorylating Smad3 during renal fibrosis 早期生长应答蛋白 2 在肾脏纤维化过程中通过磷酸化 Smad3 促进部分上皮-间质转化。

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-26 DOI: 10.1016/j.trsl.2024.04.005

Anni Song , Ruiwei Yan , Wei Xiong, Huiling Xiang, Jing Huang, Anni Jiang, Chun Zhang

{"title":"Early growth response protein 2 promotes partial epithelial-mesenchymal transition by phosphorylating Smad3 during renal fibrosis","authors":"Anni Song , Ruiwei Yan , Wei Xiong, Huiling Xiang, Jing Huang, Anni Jiang, Chun Zhang","doi":"10.1016/j.trsl.2024.04.005","DOIUrl":"10.1016/j.trsl.2024.04.005","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) is a serious health problem worldwide, which ultimately leads to end-stage renal disease (ESRD). Renal fibrosis is the common pathway and major pathological manifestation for various CKD proceeding to ESRD. However, the underlying mechanisms and effective therapies are still ambiguous. Early growth response 2 (EGR2) is reportedly involved in organ formation and cell differentiation. To determine the role of EGR2 in renal fibrosis, we respectively confirmed the increased expression of EGR2 in kidney specimens from both CKD patients and mice with location in proximal tubules. Genetic deletion of EGR2 attenuated obstructive nephropathy while EGR2 overexpression further promoted renal fibrosis in mice subjected to unilateral ureteral obstruction (UUO) due to extracellular matrix (ECM) deposition mediating by partial epithelial-mesenchymal transition (EMT) as well as imbalance between matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs). We found that EGR2 played a critical role in Smad3 phosphorylation, and inhibition of EGR2 reduced partial EMT leading to blockade of ECM accumulation in cultured human kidney 2 cells (HK2) treated with transforming growth factor β1 (TGF-β1). In addition, the transcription co-stimulator signal transducer and activator of transcription 3 (STAT3) phosphorylation was confirmed to regulate the transcription level of EGR2 in TGF-β1-induced HK2 cells. In conclusion, this study demonstrated that EGR2 played a pathogenic role in renal fibrosis by a p-STAT3-EGR2-p-Smad3 axis. Thus, targeting EGR2 could be a promising strategy for CKD treatment.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 13-25"},"PeriodicalIF":7.8,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Extra-nuclear TERT counteracts oxidative stress and promotes progression in papillary thyroid carcinoma 核外惰性物质能抵消氧化应激并促进甲状腺乳头状癌的进展

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-24 DOI: 10.1016/j.trsl.2024.04.004

Marina Muzza , Gabriele Pogliaghi , Carla Colombo , Elisa Stellaria Grassi , Erika Carbone , Sonia Palazzo , Francesco Frattini , Giacomo Gazzano , Luca Persani , Laura Fugazzola

{"title":"Extra-nuclear TERT counteracts oxidative stress and promotes progression in papillary thyroid carcinoma","authors":"Marina Muzza , Gabriele Pogliaghi , Carla Colombo , Elisa Stellaria Grassi , Erika Carbone , Sonia Palazzo , Francesco Frattini , Giacomo Gazzano , Luca Persani , Laura Fugazzola","doi":"10.1016/j.trsl.2024.04.004","DOIUrl":"10.1016/j.trsl.2024.04.004","url":null,"abstract":"<div><p>The reactivation of TERT is associated with poor outcome in papillary thyroid cancer (PTC). Extra-telomeric functions of TERT were reported, with a protective role against oxidative stress (OS). The aim of the present study was to explore the extra-nuclear TERT localization in PTC and its role in cancer progression.</p><p>TERT nuclear export under OS were analyzed in K1 PTC cell line. We investigated the role of different TERT localizations using specific TERT constructs that limit its localization to the nucleus or to the mitochondria. The effect of SRC kinase inhibitor PP2, which reduces TERT nuclear export, was investigated as well. Moreover, TERT localization was analyzed in 39 PTC tissues and correlated with the genetic profile and the level of OS, DNA damage and apoptosis in the tumors and with the clinical characteristics of the patients.</p><p>We demonstrated that TERT is exported from the nucleus in response to OS induced either from H2O2 or the BRAF inhibitor PLX4720. We proved that extra-nuclear TERT reduces mitochondrial OS and induces mitochondrial fragmentation. Moreover, limiting mitochondrial TERT localization reduced proliferation, migration, AKT phosphorylation and glycolysis and increased DNA damage and p21 expression. Finally, in PTC tissues the fraction of mitochondrial/nuclear TERT resulted inversely correlated with OS and p21 expression and associated with tumor persistence.</p><p>In conclusion, our data indicate that extra-nuclear TERT is involved in reducing the effect of excessive OS, thus promoting cancer cell survival. Extra-nuclear TERT may thus represent a marker of cancer progression and a possible therapeutic target in PTC.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"271 ","pages":"Pages 1-12"},"PeriodicalIF":7.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140765374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Inhibition of Usp14 ameliorates renal ischemia-reperfusion injury by reducing Tfap2a stabilization and facilitating mitophagy 抑制 Usp14 可降低 Tfap2a 的稳定性并促进有丝分裂，从而改善肾缺血再灌注损伤。

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-21 DOI: 10.1016/j.trsl.2024.04.002

Yang Li, Boqing Dong, Ying Wang, Huanjing Bi, Jing Zhang, Chenguang Ding, Chenge Wang, Xiaoming Ding, Wujun Xue

{"title":"Inhibition of Usp14 ameliorates renal ischemia-reperfusion injury by reducing Tfap2a stabilization and facilitating mitophagy","authors":"Yang Li, Boqing Dong, Ying Wang, Huanjing Bi, Jing Zhang, Chenguang Ding, Chenge Wang, Xiaoming Ding, Wujun Xue","doi":"10.1016/j.trsl.2024.04.002","DOIUrl":"10.1016/j.trsl.2024.04.002","url":null,"abstract":"<div><p>Mitochondrial dysfunction is recognized as a pivotal contributor to the pathogenesis of renal ischemia-reperfusion (IR) injury. Mitophagy, the process responsible for removing damaged protein aggregates, stands as a critical mechanism safeguarding cells against IR injury. Currently, the role of deubiquitination in regulating mitophagy still needs to be completely elucidated. This study aimed to evaluate the impact of ubiquitin-specific peptidase 14 (Usp14), a deubiquitinase, in IR injury by influencing mitophagy. Utilizing a murine model of renal IR injury, Usp14 silencing was found to ameliorate kidney injury, leading to decreased levels of serum creatinine and blood urea nitrogen, alongside diminished oxidative stress and inflammation. In renal epithelial cells subjected to hypoxia/reoxygenation (H/R), Usp14 knockdown increased cell viability and reduced apoptosis. Further mechanistic studies revealed that Usp14 interacted with and deubiquitinated transcription factor AP-2 alpha (Tfap2a), thereby suppressing its downstream target gene, TANK binding kinase 1 (Tbk1), to influence mitophagy. Tfap2a overexpression or Tbk1 inhibition reversed the protective effects of Usp14 silencing on renal tubular cell injury and its facilitation of mitophagy. In summary, our study demonstrated the renoprotective role of Usp14 knockdown in mitigating renal IR injury by promoting Tfap2a-mediated Tbk1 upregulation and mitophagy. These findings advocate for exploring Usp14 inhibition as a promising therapeutic avenue for mitigating IR injury, primarily by enhancing the clearance of damaged mitochondria through augmented mitophagy.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"270 ","pages":"Pages 94-103"},"PeriodicalIF":7.8,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140770206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Targeting the devil: Strategies against cancer-associated fibroblasts in colorectal cancer 瞄准恶魔针对结直肠癌中癌症相关成纤维细胞的策略

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-16 DOI: 10.1016/j.trsl.2024.04.003

Yuting Chen , Zhiyong Liang , Maode Lai

{"title":"Targeting the devil: Strategies against cancer-associated fibroblasts in colorectal cancer","authors":"Yuting Chen , Zhiyong Liang , Maode Lai","doi":"10.1016/j.trsl.2024.04.003","DOIUrl":"https://doi.org/10.1016/j.trsl.2024.04.003","url":null,"abstract":"<div><p>Cancer-associated fibroblasts (CAFs), as significant constituents of the tumor microenvironment (TME), play a pivotal role in the progression of cancers, including colorectal cancer (CRC). In this comprehensive review, we presented the origins and activation mechanisms of CAFs in CRC, elaborating on how CAFs drive tumor progression through their interactions with CRC cells, immune cells, vascular endothelial cells, and the extracellular matrix within the TME. We systematically outline the intricate web of interactions among CAFs, tumor cells, and other TME components, and based on this complex interplay, we summarize various therapeutic strategies designed to target CAFs in CRC. It is also essential to recognize that CAFs represent a highly heterogeneous group, encompassing various subtypes such as myofibroblastic CAF (myCAF), inflammatory CAF (iCAF), antigen-presenting CAF (apCAF), vessel-associated CAF (vCAF). Herein, we provide a summary of studies investigating the heterogeneity of CAFs in CRC and the characteristic expression patterns of each subtype. While the majority of CAFs contribute to the exacerbation of CRC malignancy, recent findings have revealed specific subtypes that exert inhibitory effects on CRC progression. Nevertheless, the comprehensive landscape of CAF heterogeneity still awaits exploration. We also highlight pivotal unanswered questions that need to be addressed before CAFs can be recognized as feasible targets for cancer treatment. In conclusion, the aim of our review is to elucidate the significance and challenges of advancing in-depth research on CAFs, while outlining the pathway to uncover the complex roles of CAFs in CRC and underscore their significant potential as therapeutic targets.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"270 ","pages":"Pages 81-93"},"PeriodicalIF":7.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140645641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Retraction notice to “Transfer of microRNA-221 from mesenchymal stem cell-derived extracellular vesicles inhibits atherosclerotic plaque formation” [Transl. Res. 226 (2020) 83–95] 间充质干细胞衍生的细胞外囊泡转移 microRNA-221 可抑制动脉粥样硬化斑块形成》的撤稿通知 [Transl. Res. 226 (2020) 83-95]

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-11 DOI: 10.1016/j.trsl.2024.03.010

Ziyuan Guo, Zhuo Zhao, Chuang Yang, Chunli Song

引用次数: 0

Exosomal Tenascin-C primes macrophage pyroptosis amplifying aberrant inflammation during sepsis-induced acute lung injury 在脓毒症诱发急性肺损伤期间，外泌体Tenascin-C可激发巨噬细胞的脓毒症，放大异常炎症反应

IF 7.8 2区医学

Translational Research Pub Date : 2024-04-09 DOI: 10.1016/j.trsl.2024.04.001

Ting Gong , Xuedi Zhang , Xiaolei Liu , Yinfeng Ye , Zhiyuan Tian , Shuang Yin , Min Zhang , Jing Tang , Youtan Liu

{"title":"Exosomal Tenascin-C primes macrophage pyroptosis amplifying aberrant inflammation during sepsis-induced acute lung injury","authors":"Ting Gong , Xuedi Zhang , Xiaolei Liu , Yinfeng Ye , Zhiyuan Tian , Shuang Yin , Min Zhang , Jing Tang , Youtan Liu","doi":"10.1016/j.trsl.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.trsl.2024.04.001","url":null,"abstract":"<div><p>Sepsis-induced acute lung injury (ALI) is a serious complication of sepsis and the predominant cause of death. Exosomes released by lung tissue cells critically influence the progression of ALI during sepsis by modulating the inflammatory microenvironment. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbates ALI in septic infection remain undefined. Our study found increased levels of exosomal Tenascin-C (TNC) in the plasma of both patients and mice with ALI, showing a strong association with disease progression. By integrating exosomal proteomics with transcriptome sequencing and experimental validation, we elucidated that LPS induce unresolved endoplasmic reticulum stress (ERs) in alveolar epithelial cells (AECs), ultimately leading to the release of exosomal TNC through the activation of PERK-eIF2α and the transcription factor CHOP. In the sepsis mouse model with TNC knockout, we noted a marked reduction in macrophage pyroptosis. Our detailed investigations found that exosomal TNC binds to TLR4 on macrophages, resulting in an augmented production of ROS, subsequent mitochondrial damage, activation of the NF-κB signaling pathway, and induction of DNA damage response. These interconnected events culminate in macrophage pyroptosis, thereby amplifying the release of inflammatory cytokines. Our findings demonstrate that exosomal Tenascin-C, released from AECs under unresolved ER stress, exacerbates acute lung injury by intensifying sepsis-associated inflammatory responses. This research provides new insights into the complex cellular interactions underlying sepsis-induced ALI.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"270 ","pages":"Pages 66-80"},"PeriodicalIF":7.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000781/pdfft?md5=2d42ae76da3f6c18a73fcdc3dafc0858&pid=1-s2.0-S1931524424000781-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140619981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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