JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"Downregulation of Alox5 Inhibits Ferroptosis to Improve Doxorubicin-Induced Cardiotoxicity via the P53/SLC7A11 Pathway","authors":"Wenxi Fang,&nbsp;Zhefu Hu,&nbsp;Bo Shen,&nbsp;Xiaofeng Zeng,&nbsp;Si Chen,&nbsp;Shasha Wang,&nbsp;Saiyang Xie,&nbsp;Wei Deng","doi":"10.1111/jcmm.70641","DOIUrl":"https://doi.org/10.1111/jcmm.70641","url":null,"abstract":"<p>Doxorubicin (DOX) is an anthracycline chemotherapeutic drug used for tumour treatment. Due to DOX-induced cardiotoxicity (DIC), its clinical application has been widely limited. Multiple studies have shown that ferroptosis is involved in the pathogenesis of DIC and that arachidonate 5-lipoxygenase (Alox5) plays an important role in the occurrence and development of ferroptosis. The aim of this study was to provide evidence that silencing Alox5 alleviated DIC by affecting ferroptosis and identify mechanisms. Acute models of DIC were established in wild-type (WT) C57BL/6 and Alox5-deficient (Alox5 KO) mice and neonatal rat ventricular myocytes (NRVMs). Alox5 was upregulated in vivo and in vitro during DIC. Subsequently, we overexpressed the Alox5 gene in adult mice using a recombinant adenovirus expression vector (rAAV9). Compared with that in WT mice, overexpressing Alox5 accelerated DOX-induced myocardial injury and cardiac dysfunction. This finding was also confirmed in vitro. In contrast, silencing the Alox5 gene protected against myocardial injury in the DIC model and reduced ferroptosis and inflammation, and this effect was confirmed in vitro. In addition, transcriptomics and GO enrichment analysis of adult mouse cardiomyocytes showed that Alox5 could ameliorate DIC by inhibiting ferroptosis and inflammation. Moreover, P53 was identified as a target of Alox5. Subsequently, in vivo and in vitro experiments showed that silencing Alox5 could alleviate ferroptosis and inflammation. Further in vivo and in vitro experiments demonstrated that dexrazoxane (DXZ) could ameliorate DIC caused by Alox5 overexpression by alleviating ferroptosis. Mechanistically, silencing Alox5 could reduce reactive oxygen species (ROS) production through the P53/SLC7A11 pathway. Furthermore, P53 inhibitors significantly inhibited the adverse effects of Alox5 overexpression on DIC. The final experiment showed that pharmacological inhibition of Alox5 could prevent DIC in vivo and in vitro. Our study showed that the downregulation of Alox5 alleviated myocardial damage associated with DIC via the P53/SLC7A11 pathway. Therefore, inhibiting Alox5 might be a potential strategy for the treatment of DIC.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Succinate Accumulation Accelerates Oxidative Stress to Promote Pulmonary Epithelial Cell Apoptosis During Lung Ischemia–Reperfusion Injury","authors":"Wenhao Wang,&nbsp;Nana Feng,&nbsp;Qi Shi,&nbsp;Jichun Yang,&nbsp;Yulong Tan,&nbsp;Wenyong Zhou,&nbsp;Meng Shi","doi":"10.1111/jcmm.70645","DOIUrl":"https://doi.org/10.1111/jcmm.70645","url":null,"abstract":"<p>During ischemia, succinate accumulates and leads to significant damage to the tissues. The specific role of succinate in lung ischemia–reperfusion injury (LIRI) remains unresolved. Differential metabolites in LIRI were identified through untargeted metabolomics using gas chromatography–mass spectrometry (GC–MS). Type II alveolar epithelial cells (AECs) were cultured and subjected to hypoxia/reoxygenation (H/R) in vitro, while an in vivo LIRI model was developed using C57BL/6 mice. Cytokine levels, lung oedema, histopathological alterations and lung functionality were evaluated. Protein levels were analysed through Western blotting. The mitochondrial membrane potential (Δψm) was measured using the JC-1 fluorescent dye, and mitochondrial morphology in Type II AECs following H/R damage was observed with a transmission electron microscope (TEM). Oxidative stress and apoptosis markers were detected in lung tissues and Type II AECs. Succinate was increased in the peripheral serum of LIRI patients and the C57BL/6 mices model. Succinate pre-treatment promotes Type II AEC cell apoptosis and oxidative stress, inhibits mitochondrial membrane potential and damages the alveolar epithelial cells' mitochondrial activity after H/R. Meanwhile, succinate may considerably reduce the amounts of acyl-CoA oxidase 1 (ACOX1) and isocitrate dehydrogenase 2 (IDH2) protein expression. Importantly, N-acetyl-L-cysteine (NAC) was observed to dramatically retard succinate-induced cell apoptosis, mitochondrial dysfunction and ROS levels in alveolar epithelial cells following H/R in vivo, with succinate-neutralising antibodies protecting LIRI in vitro. In conclusion, during ischemia, the build-up of succinate contributes to the advancement of LIRI by enhancing mitochondrial oxidative stress and promoting cell apoptosis, and blocking succinate may be a potential target for LIRI treatment.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70645","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Adalimumab on Mitochondria of Psoriatic Mesenchymal Stem Cells","authors":"Mariangela Di Vincenzo,&nbsp;Anna Campanati,&nbsp;Giulia Cannelonga,&nbsp;Federico Diotallevi,&nbsp;Giorgia Cerqueni,&nbsp;Andrea Marani,&nbsp;Saverio Marchi,&nbsp;Monia Orciani","doi":"10.1111/jcmm.70642","DOIUrl":"https://doi.org/10.1111/jcmm.70642","url":null,"abstract":"<p>Psoriasis is a systemic immune-mediated disorder involving multiple signalling pathways. Recent attempts to treat psoriasis involve monoclonal antibodies that block different inflammatory pathways. The monoclonal antibody Adalimumab (ADM) is one of the biologics that block the inflammatory cascade of TNF-alpha. We previously demonstrated the involvement of mesenchymal stem cells (MSCs) in psoriasis pathogenesis and showed their responsiveness to ADM, highlighting their dual role as contributors and therapeutic targets. Mitochondrial dysfunction is increasingly recognised in psoriasis, contributing to oxidative stress, altered metabolism, and immune dysregulation. These mitochondrial changes drive chronic inflammation, keratinocyte hyperproliferation, and immune activation—hallmarks of psoriasis—making mitochondria a key focus for therapeutic strategies. In this study, we further investigated ADM's impact on mitochondrial morphology and function in MSCs. MSCs were isolated from the skin of psoriatic patients (PSO-MSCs) and healthy controls (C-MSCs), then exposed to H₂O₂ or LPS to mimic the oxidative and inflammatory environment of psoriasis. PSO-MSCs were also treated with ADM for 72 h before mitochondrial analysis. Compared to C-MSCs, PSO-MSCs showed marked mitochondrial abnormalities. ADM treatment partially reversed these alterations, restoring mitochondrial parameters toward control levels under basal conditions. However, ADM failed to prevent mitochondrial dysfunction when additional stress (H₂O₂ or LPS) was introduced. In conclusion, ADM exerts a protective effect on mitochondrial health in MSCs from psoriatic patients, suggesting mitochondria are among its therapeutic targets. Nonetheless, ADM alone cannot counteract further environmental or inflammatory stressors, which may explain symptom relapse observed in clinical settings.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70642","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering Deleterious nsSNPs in MUC16's SEA Domain: Structural and Functional Implications in Cancer Metastasis via Computational Analysis","authors":"Muaz Faruque,&nbsp;Maisha Maliha Medha,&nbsp;A. M. U. B. Mahfuz,&nbsp;Md. Monirul Islam,&nbsp;Md Afjalus Siraj","doi":"10.1111/jcmm.70633","DOIUrl":"https://doi.org/10.1111/jcmm.70633","url":null,"abstract":"<p>MUC16 ranks among the top three genes exhibiting the highest mutation frequencies in various cancer types. It encodes transmembrane mucins present in the epithelial linings of the ocular, respiratory, gastric and female reproductive systems, serving to protect and maintain mucosal surfaces. Overexpression of MUC16 contributes to the differentiation, proliferation, invasion and metastasis of cancer cells in ovarian, endometrial, pancreatic, colon, breast and non-small-cell lung cancers. In this study, we analysed the structural and functional effects of pathogenic and potentially harmful non-synonymous single nucleotide polymorphisms (nsSNPs) of MUC16, employing a blend of computational algorithms. Initially, SNPs data for MUC16 were gathered from the Ensembl database and refined using computational tools (PROVEAN, SIFT, PolyPhen-2, SNAP-2, MutPred, I-Mutant3.0 and MUpro) to isolate four final pathogenic SNP variants (L151P, Y144N, C111Y and D108Y). Through evolutionary conservation analysis, we determined that these mutational variants originate from a highly conserved and stable domain. Our findings particularly emphasise the Y144N variant as a potentially highly deleterious mutation situated in the SEA5 domain. This variant could significantly impact stability, overall flexibility, compactness, expansion, glycosylation ability and metastatic potential when compared to both the wild-type and other mutant variants. In summary, these findings shed light on missense mutational variants, providing insights into the vast array of disease susceptibilities associated with MUC16's glycosylation process. This understanding could aid in the development of effective drugs for diseases linked with these mutations.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70633","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIB2-Mediated SUZ12 Ubiquitination Regulates Clonal Proliferation in Patients With Paroxysmal Nocturnal Haemoglobinuria","authors":"Hui Liu,&nbsp;Lijie Zeng,&nbsp;Chaomeng Wang,&nbsp;Yingying Chen,&nbsp;Liyan Li,&nbsp;Zhaoyun Liu,&nbsp;Honglei Wang,&nbsp;Rong Fu","doi":"10.1111/jcmm.70597","DOIUrl":"https://doi.org/10.1111/jcmm.70597","url":null,"abstract":"<p>Secondary gene mutations are one of the main mechanisms underlying paroxysmal nocturnal haemoglobinuria (PNH) clone proliferation. Our previous studies showed that SUZ12 participates in PNH clone proliferation by regulating H3K27me3. However, the mechanism underlying the SUZ12 function remains unclear. Immunoprecipitation and mass spectrometry were used to identify SUZ12 interacting proteins in <i>PIGA</i>-KO K562 cells. Furthermore, RNA-seq was used to explore the signalling pathways. Finally, colony formation assays, western blotting, and flow cytometry were performed to determine the proliferative ability of the cells. We identified 59 potential proteins that interact with SUZ12 and revealed a physical interaction between MIB2 and SUZ12 exclusively in the K562-KO cell line. Furthermore, we emphasise the vital involvement of the MIB/HERC and ZZ-type domains in the physical association between MIB2 and SUZ12. After MIB2 knockdown, SUZ12 protein decreased while the ubiquitination levels of SUZ12 were enhanced. Additionally, PRC2-related target genes were upregulated in the siMIB2 group. SUZ12 and H3K27me3 expression levels and cell proliferation significantly decreased after MIB2 knockdown, whereas cell apoptosis significantly increased. MIB2 protein levels are also elevated in patients with PNH. In conclusion, MIB2 affects the stability of the PRC2 complex by mediating SUZ12 ubiquitination, which in turn regulates PNH clone proliferation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70597","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Combining r-ATG With PTCy for GvHD Prophylaxis in Haploidentical HSC Transplantation for Malignancies—A Systematic Review","authors":"Joseph M. John,&nbsp;Uday Kulkarni,&nbsp;Dinesh Pendharkar,&nbsp;Sachin Jadhav","doi":"10.1111/jcmm.70450","DOIUrl":"https://doi.org/10.1111/jcmm.70450","url":null,"abstract":"<p>Allogeneic haematopoietic stem cell transplantation (HSCT) for haematological malignancies can cause acute and chronic graft-versus-host disease (GvHD), impacting graft success and mortality. Rabbit anti-thymocyte globulin (r-ATG) or post-transplant cyclophosphamide (PTCy) is effective in reducing GvHD in haploidentical-HSCT. This review included 17 studies to assess rATG + PTCy for GvHD prophylaxis. Overall acute GvHD grade II-IV, moderate-to-severe chronic GvHD and GvHD-free relapse-free survival rates ranged from 11.50%–35.40%, 2.90%–17.78% and 21.80%–63%, respectively. Although r-ATG + PTCy treatment lowered GvHD incidence and increased survival rates, cytomegalovirus and Epstein–Barr virus reactivation were observed; therefore, more investigations on this treatment are needed, especially on dosing and timing when used for HSCT.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70450","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Randomized Clinical Trial of Continuous Transversus Thoracis Muscle Plane Block for Patients Undergoing Open Heart Valve Replacement Surgery”","authors":"","doi":"10.1111/jcmm.70648","DOIUrl":"https://doi.org/10.1111/jcmm.70648","url":null,"abstract":"<p>Zhan Y, Li L, Chen S, Peng Y, Zhang Y. Randomized Clinical Trial of Continuous Transversus Thoracis Muscle Plane Block for Patients Undergoing Open Heart Valve Replacement Surgery. <i>J Cell Mol Med</i>. 2024; 28:e18184. doi: 10.1111/jcmm.18184.</p><p>In the article, references 12, 13, 14, 17, and 18 were incorrect and should be replaced.</p><p>The incorrect references are:</p><p>12. Ueshima H, Otake H. Continuous transversus thoracic muscle plane block is effective for the median sternotomy. <i>J Clin Anesth</i>. 2017;37:174.</p><p>13. Ueshima H, Otake H. Where is an appropriate injection point for an ultrasound-guided transversus thoracic muscle plane block? <i>J Clin Anesth</i>. 2016;33:190-191.</p><p>14. Ueshima H, Takeda Y, Ishikawa S, Otake H. Ultrasound-guided transversus thoracic muscle plane block: a cadaveric study of the spread of injectate. <i>J Clin Anesth</i>. 2015;27:696.</p><p>17. Ueshima H, Hara E, Marui T, Otake H. The ultrasound-guided transversus thoracic muscle plane block is effective for the median sternotomy. <i>J Clin Anesth</i>. 2016;29:8.</p><p>18. Ueshima H, Otake H. Ultrasound-guided transversus thoracic muscle plane block: complication in 299 consecutive cases. <i>J Clin Anesth</i>. 2017;41:60.</p><p>The correct references are:</p><p>12. Avneet Singh, Indumati, Dheeraj Kapoor, Suman Dhillon, Jasmine K Narula, Sidharth Garg. Continuous Bilateral Transversus Thoracic Muscle Plane Block: An Analgesia Boon for Scoliotic Patients Undergoing Cardiac Surgery. <i>Ann Card Anaesth</i>. 2024 Jan 1;27(1):61-64.</p><p>13. Samerchua Artid, Leurcharusmee Prangmalee, Supphapipat Kittitorn, Unchiti Kantarakorn, Lapisatepun Panuwat, Maikong Naraporn, Kantakam Perada, Navic Pagorn, Mahakkanukrauh Pasuk. Optimal techniques of ultrasound-guided superficial and deep parasternal intercostal plane blocks: a cadaveric study. <i>Region Anesth Pain</i> M. 2024-05-07;49(5):320-325.</p><p>14. Harbell Monica W, Langley Natalie R, Seamans David P, Kraus Molly B, Carey Frederick J, Craner Ryan C.Deep parasternal intercostal plane nerve block: an anatomical study. <i>Region Anesth Pain</i> M. 2024-03-04;49(3):179-183.</p><p>17. Mohamed Ahmed Hamed, Maged Labib Boules, Mina Mahrou Sobhy, Mahdy Ahmed Abdelhady.The Analgesic Efficacy of Ultrasound-Guided Bilateral Transversus Thoracic Muscle Plane Block After Open-Heart Surgeries: A Randomized Controlled Study.<i>J Pain Res</i>. 2022-01-01;15:675-682.</p><p>18. Jian-Jun Xue, Yi-Yang Cui, Jason W Busse, Long Ge, Ting Zhou, Wei-Hua Huang, Sheng-Shuang Ding, Jie Zhang, Ke-Hu Yang. Transversus thoracic muscle plane block for pain during cardiac surgery: a systematic review and meta-analysis. <i>Int J Surg</i>. 2023 Aug 1;109(8):2500-2508.</p><p>The online version of the article was corrected.</p><p>We apologize for these errors.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Approaches to NAFLD: Exploring the Role of Nicotinamide in Multicellular Microtissue Models of Liver Fibrosis","authors":"Farnaz Sani,&nbsp;Shima Parsa,&nbsp;Kimia Falamarzi,&nbsp;Mohammadhossein Khorraminejad-Shirazi,&nbsp;Negar Azarpira,&nbsp;Mahsa Sani","doi":"10.1111/jcmm.70606","DOIUrl":"https://doi.org/10.1111/jcmm.70606","url":null,"abstract":"<p>In non-alcoholic fatty liver disease (NAFLD), characterised by progressive liver damage, inflammation, fibrosis and potential cirrhosis, treatment options are limited, with liver transplantation as the only definitive solution. To address this urgent need, in vitro and tissue engineering studies have explored new drugs. This study investigated the anti-inflammatory and anti-fibrotic potential of Nicotinamide, utilising promising preliminary data for treating NAFLD. Multicellular liver microtissues comprising LX2 stellate cells, HepG2 hepatocytes and HUVECs were generated to establish a robust preclinical model for fibrosis. Cell viability and histological assessments confirmed successful co-aggregation within the microtissues. To induce fibrosis, they were treated with a palmitic and oleic acid mixture, followed by exposure to Nicotinamide. Treatment effectiveness was evaluated by analysing inflammatory factors, including transforming growth factor β1 (TGF-β1), tumour necrosis factor-alpha (TNF-α) and interleukin 1 beta and interleukin 6. Extracellular matrix deposition was assessed by measuring collagen type I (COL I) and α-smooth muscle actin (α-SMA). Our data suggested that Nicotinamide application led to significant improvements across several measures. Specifically, it effectively reduced inflammatory response by reducing TGF-β1 levels and decreasing COL I and α-SMA levels. Furthermore, Nicotinamide was crucial in reducing reactive oxygen species levels, indicating that activation of HSC, inflammatory signals and oxidative stress work together. These in vitro findings suggest Nicotinamide may have therapeutic potential warranting further investigation in advanced preclinical models. Our findings demonstrated significant improvements across various parameters, including reduced expression of pro-inflammatory cytokines and attenuated oxidative stress, underscoring the therapeutic potential of Nicotinamide in clinical studies.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70606","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Growth Differentiation Factor 15 Induces Gastric Fundus Contraction Involving Cholinergic Excitation: Morphofunctional Evidence in Rodent Models","authors":"Rachele Garella,&nbsp;Francesco Palmieri,&nbsp;Livio Tarchi,&nbsp;Alessia Tani,&nbsp;Flaminia Chellini,&nbsp;Giulia Guarnieri,&nbsp;Annamaria Morelli,&nbsp;Caterina Bernacchioni,&nbsp;Paolo Rovero,&nbsp;Valdo Ricca,&nbsp;Giovanni Castellini,&nbsp;Chiara Sassoli,&nbsp;Roberta Squecco","doi":"10.1111/jcmm.70629","DOIUrl":"https://doi.org/10.1111/jcmm.70629","url":null,"abstract":"<p>Growth Differentiation Factor 15 (GDF15) is a peptide from the transforming growth factor (TGF)-β superfamily, typically found at low levels in mammalian tissues, but significantly upregulated during cellular stress or injury. Initially recognised for its role in inducing anorexia and vomiting, GDF15 is now seen as a broader regulator of homeostasis, although its effects on gastrointestinal function remain unclear. This study examined GDF15's impact on the gastric fundus, a key region for appetite regulation. In ex vivo rodent gastric smooth muscle, GDF15 receptors were detected, and exposure to GDF15 caused smooth muscle depolarization, leading to increased mechanical activation. Morphological analyses revealed changes in the contractile apparatus, resembling cholinergic excitatory pathways. These effects were blocked by atropine, indicating muscarinic receptor involvement. Taken together, these findings suggest that GDF15 enhances gastric contractility by influencing cholinergic tone. Further studies will shed light on its mechanism of action and on the potential translational perspective of current results, elucidating whether elevated plasma levels of GDF15 observed in several physiological and pathological conditions can also have repercussions in gastric physiology, appetite regulation and weight loss.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70629","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"STAT3 Facilitates Super Enhancer Formation to Promote Fibroblast-To-Myofibroblast Differentiation by the Analysis of ATAC-Seq, RNA-Seq and ChIP-Seq","authors":"Yujie Wang,&nbsp;Yaqin Zhao,&nbsp;Guohong Cao,&nbsp;Mengqi Jiang,&nbsp;Xinglong Yuan,&nbsp;Hongbo Li,&nbsp;Xiaodong Song,&nbsp;Jinjin Zhang,&nbsp;Changjun Lv,&nbsp;Songzi Zhang","doi":"10.1111/jcmm.70639","DOIUrl":"https://doi.org/10.1111/jcmm.70639","url":null,"abstract":"<p>A cellular characteristic of IPF is the transformation of fibrosis into myofibroblasts. This study identifies several transcription factors—STAT3, FOXP1, JUNB, ATF3, FosL2, BATF, Fra2 and AP-1—that play crucial roles in promoting pulmonary fibrogenesis. They achieve this by facilitating the differentiation of fibroblasts into myofibroblasts, as analysed through ATAC-seq and RNA-seq. Additionally, STAT3 ChIP-seq showed that STAT3 is significantly concentrated in accessible chromatin regions, including introns and intergenic areas. H3K27ac ChIP-seq and Co-IP demonstrated that STAT3 plays a role in the formation of super enhancer (SE), which promotes gene expression. CUT&amp;RUN-qPCR and the pGL3-SE dual-luciferase reporter system assays proved that STAT3 enhanced pGL3-SE activities by facilitating H3K27ac modification, leading to promoting the transcription of target genes including RUNX1, JUNB, JUN, SMAD6, COL3A1 and PTPN1. In summary, this study shows that STAT3 contributes to the formation of SEs that accelerate the differentiation of fibroblasts into myofibroblasts, leading to IPF. This insight enhances our understanding of STAT3-related SEs and offers potential therapeutic strategies for fibrotic diseases.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"29 11","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}