International journal of molecular medicine最新文献

{"title":"Role of GLP‑1 receptor agonists in sepsis and their therapeutic potential in sepsis‑induced muscle atrophy (Review).","authors":"Xuan Zhao, Yukun Liu, Dongfang Wang, Tonghan Li, Zhikai Xu, Zhanfei Li, Xiangjun Bai, Yuchang Wang","doi":"10.3892/ijmm.2025.5515","DOIUrl":"10.3892/ijmm.2025.5515","url":null,"abstract":"<p><p>Sepsis‑induced myopathy (SIM) is a common complication in intensive care units, which is often associated with adverse outcomes, primarily manifested as skeletal muscle weakness and atrophy. Currently, the management of SIM focuses on prevention strategies, as effective therapeutic options remain elusive. Glucagon‑like peptide‑1 (GLP‑1) receptor agonists (GLP‑1RAs) have garnered attention as hypoglycemic and weight‑loss agents, with an increasing body of research focusing on the extrapancreatic effects of GLP‑1. In preclinical settings, GLP‑1RAs exert protective effects against sepsis‑related multiple organ dysfunction through anti‑inflammatory and antioxidant mechanisms. Based on the existing research, we hypothesized that GLP‑1RAs may serve potential protective roles in the repair and regeneration of skeletal muscle affected by sepsis. The present review aimed to explore the relationship between GLP‑1RAs and sepsis, as well as their impact on muscle atrophy‑related myopathy. Furthermore, the potential mechanisms and therapeutic benefits of GLP‑1RAs are discussed in the context of muscle atrophy induced by sepsis.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of lysine lactylation in neoplastic and inflammatory pulmonary diseases (Review).","authors":"Shanshan Wang, Hongyan Zheng, Jianping Zhao, Jungang Xie","doi":"10.3892/ijmm.2025.5512","DOIUrl":"10.3892/ijmm.2025.5512","url":null,"abstract":"<p><p>Protein lysine lactylation is a ubiquitous and post‑translational modification of lysine residues that involves the addition of a lactyl group on both histone and non‑histone proteins. This process plays a pivotal role in human health and disease and was first discovered in 2019. This epigenetic modification regulates gene transcription from chromatin or directly influences non‑histone proteins by modulating protein‑DNA/protein interactions, activity and stability. The dual functions of lactylation in both histone and non‑histone proteins establish it as a crucial mechanism involved in various cellular processes, such as cell proliferation, differentiation, immune and inflammatory responses and metabolism. Specific enzymes, referred to as 'writers' and 'erasers', catalyze the addition or removal of lactyl groups at designated lysine sites, thereby dynamically modulating lactylation through alterations in their enzymatic activities. The respiratory system has a remarkably intricate metabolic profile. Numerous pulmonary diseases feature an atypical transition towards glycolytic metabolism, which is linked to an overproduction of lactate, a possible substrate for lactylation. However, there has yet to be a comprehensive review elucidating the full impact of lactylation on the onset, progression and potential treatment of neoplastic and inflammatory pulmonary diseases. In the present review, an extensive overview of the discovery of lactylation and advancements in research on the existing lactylation sites were discussed. Furthermore, the review particularly investigated the potential roles and mechanisms of histone and non‑histone lactylation in various neoplastic and inflammatory pulmonary diseases, including non‑small cell lung cancers, malignant pleural effusion, pulmonary fibrosis, acute lung injury and asthma, to excavate the new therapeutic effects of post‑translational modification on various pulmonary diseases.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Corrigendum] Use of methylation profiling to identify significant differentially methylated genes in bone marrow mesenchymal stromal cells from acute myeloid leukemia.","authors":"Jing Huang, Zhi Liu, Yufan Sun, Qi Zhong, Li Xu, Ruimin Ou, Cheng Li, Rui Chen, Mengdong Yao, Qing Zhang, Shuang Liu","doi":"10.3892/ijmm.2025.5520","DOIUrl":"10.3892/ijmm.2025.5520","url":null,"abstract":"<p><p>Following the publication of the above article, an interested reader drew to the authors' and the Editor's attention that, given the subject matter of the article, in a few places in the text throughout the paper, 'MIR159' was probably intended to have been written as 'MIR596', and 'miR‑159' was probably meant to have been written as 'miR‑596'. The authors have responded to confirm that the interested reader was correct in their assessment; this paper discusses the role of miR‑596 in the context of acute myeloid leukemia (AML) and its potential as a biomarker, and this error appears to have occurred during the final stages of manuscript preparation. Therefore, the following corrections to the text of this article should be noted:  a) In the final sentence of the Abstract on p. 679, 'miR‑596' should have been written, rather than 'miR‑159'. The corrected sentence should read as follows: 'Furthermore, the aberrantly hypermethylated <b>miR‑596</b>‑encoding gene <i><b>MIR596</b></i> may be a potential biomarker of AML.' b) In the Discussion, all instances where 'miR‑159' and 'MIR159' were mentioned should be corrected to 'miR‑596' and 'MIR596', respectively. The sentences concerned should have read as follows (p. 685, right‑hand column, line 9): 'Thus, it was suggested that the hypermethylation of <b>miR‑596</b> may be associated with its transcriptional regulation. It was also inferred that <b>miR‑596</b> methylation in BM‑MSCs may be a biomarker or prognostic factor for patients with AML. However, the significance of the methylation of miR‑596 demands further investigation.\" In addition, the sentence starting on p. 685, right‑hand column, second paragraph, line 5, should have read as follows: 'Furthermore, the aberrant hypermethylated <b>miR‑596</b>‑encoding gene <i><b>MIR596</b></i> may be a potential biomarker of AML.' All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine  41: 679‑686, 2018; DOI: 10.3892/ijmm.2017.3271].</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 5","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of STAT3 signaling in preeclampsia (Review).","authors":"Daniela Marzioni, Federica Piani, Nicoletta Di Simone, Stefano Raffaele Giannubilo, Andrea Ciavattini, Giovanni Tossetta","doi":"10.3892/ijmm.2025.5499","DOIUrl":"10.3892/ijmm.2025.5499","url":null,"abstract":"<p><p>Placentation is a key process that is tightly regulated that ensures the normal placenta and fetal development. Preeclampsia (PE) is a hypertensive pregnancy‑associated disorder characterized by increased oxidative stress and inflammation. STAT3 signaling plays a key role in modulating important processes such as cell proliferation, differentiation, invasion and apoptosis. The present review aimed to analyse the role of STAT3 signaling in PE pregnancies, discuss the main natural and synthetic compounds involved in modulation of this signaling both <i>in vivo</i> and <i>in vitro</i> and summarize the main cellular modulators of this signaling to identify possible therapeutic targets and treatments to improve the outcome of PE pregnancies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomics and proteomics characterizing the antioxidant mechanisms of semaglutide in diabetic mice with cognitive impairment.","authors":"Ying Yang, Lulu Song, Liping Yu, Jinping Zhang, Bo Zhang","doi":"10.3892/ijmm.2025.5497","DOIUrl":"10.3892/ijmm.2025.5497","url":null,"abstract":"<p><p>The aim of the present study was to investigate the neuroprotective effects of semaglutide in diabetes‑associated cognitive decline (DACD), while also exploring the underlying mechanisms targeting anti‑oxidative effects. The present study evaluated the antioxidant properties of semaglutide using a DACD model of inflammation. To investigate the underlying mechanisms, omics technologies were employed. Comprehensive transcriptomic and proteomic analysis of the cells was conducted to identify the pathways responsible for the observed antioxidant effects. Semaglutide demonstrated the potential to enhance learning and memory functions while mitigating hippocampal pathological damage. RNA‑sequencing and data‑independent acquisition proteomics analyses identified 13,511 differentially expressed genes and 588 differentially expressed proteins between the control and type 2 diabetes mellitus (T2DM) groups. In addition, 1,378 genes and 2,394 proteins exhibited a differential expression between the T2DM and semaglutide (10 µg/kg) treatment groups. A combined transcriptomic and proteomic analysis unveiled 40 common pathways. Acyl‑CoA oxidase 1 (ACOX1) was observed to be activated during oxidative stress and subsequently suppressed by semaglutide. Of note, the antioxidant and anti‑apoptotic properties of semaglutide in high glucose (HG) conditions were partially reversed upon ACOX1 overexpression. Overall, the present data provided molecular evidence to elucidate the physiological connections between semaglutide and neuronal function, and contribute to clarifying the role of semaglutide in combating oxidative stress and HG‑induced cognitive impairment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p23 protects against ferroptosis of brain microvascular endothelial cells in ischemic stroke.","authors":"Yao Zhao, Yunfei Xu, Qing Xu, Nina He, Jie Zhao, Ying Liu","doi":"10.3892/ijmm.2025.5505","DOIUrl":"10.3892/ijmm.2025.5505","url":null,"abstract":"<p><p>Ferroptosis is a type of iron‑dependent regulated cell death that differs from apoptosis, autophagy or necrosis. p23 serves as a co‑chaperone and performs a unique biological function in various diseases by binding to client proteins to modulate their biological functions; however, its effect on ferroptosis remains largely unknown. In the present study, the effects of cerebral ischemia/reperfusion (I/R) injury (CIRI) or oxygen‑glucose deprivation/reoxygenation on the blood‑brain barrier (BBB) and ferroptosis in brain microvascular endothelial cells (BMECs), as well as the expression of p23, were examined. Subsequently, the effects of p23 on CIRI‑induced BBB dysfunction and BMEC ferroptosis were determined. Finally, the role of glutathione peroxidase 4 (GPX4) in the regulatory effects of p23 on ferroptosis was detected. The results revealed that p23 protected against BBB injury caused by CIRI by inhibiting ferroptosis in BMECs. The effect of p23 on ferroptosis was then explored, and it was found that the expression of GPX4, a major regulator of ferroptosis, was promoted by p23. Furthermore, molecular docking and co‑immunoprecipitation experiments revealed that p23 could bind to GPX4 through its N‑terminal domain (1‑90aa), enhance the stability of GPX4 and inhibit the degradation of GPX4 by cycloheximide. Finally, a cerebral I/R animal model was established using GPX4 conditional knockout mice (GPX4 Fos^CreERT2/+), and it was revealed that the protective effect of p23 overexpression on the BBB in GPX4 Fos^CreERT2/+ mice was attenuated compared with that in GPX4 Fos^CreERT2/‑ mice. In conclusion, p23 may serve a protective role against cerebral I/R‑induced BBB injury by inhibiting ferroptosis in BMECs through enhancing the stability of GPX4, providing a potential therapeutic target for ischemic stroke.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel and promising therapeutic approach for treating pancreatic cancer: Nectin‑4‑targeted antibody‑drug conjugates alone or combined with autophagy inhibitors.","authors":"Rong Fu, Chunbin Wang, Tongjin Yin, Xuyao Zhang, Ying Xu, Yue Shi, Jing Xu, Wei Zhang, Zhe Ding","doi":"10.3892/ijmm.2025.5507","DOIUrl":"10.3892/ijmm.2025.5507","url":null,"abstract":"<p><p>Antibody‑drug conjugates (ADCs) are rapidly advancing the treatment of solid tumors, and Nectin‑4‑targeted ADCs have been approved by the FDA to treat certain cancers. Although Nectin‑4 is overexpressed in the tissues of patients with pancreatic cancer, whether Nectin‑4‑targeted ADCs can effectively treat pancreatic cancer remains unclear. The present study evaluated the therapeutic effects and mechanisms of Nectin‑4‑targeted ADCs in pancreatic cancer. A Nectin‑4‑directed ADC was chosen, Nectin‑4‑MMAE, which triggered apoptosis and induced cell death in the Nectin‑4‑positive pancreatic cancer cell lines BxPC‑3 and YAPC. Nectin‑4‑MMAE also induced autophagy in BxPC‑3 and YAPC cells by inactivating the AKT/mTOR pathway. The entire autophagy process was observed by electron microscopy and laser confocal microscopy. The autophagy inhibitors LY294002 and chloroquine significantly increased the lethal effects of Nectin‑4‑MMAE on BxPC‑3 and YAPC cells by inducing apoptosis. In the xenograft tumor model, Nectin‑4‑MMAE alone elicited potent antitumor effects. When Nectin‑4‑MMAE was combined with autophagy inhibitors, the tumor burden of mice was decreased compared with treatment with either drug alone. The present study confirmed the potent therapeutic effects of Nectin‑4‑MMAE against pancreatic cancer, and its unique antitumor mechanism provides new approaches to treatment.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143523485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remimazolam alleviates myocardial ischemia/reperfusion injury and inflammation via inhibition of the NLRP3/IL‑1β pathway in mice.","authors":"Xueru Liu, Guojing Shui, Yan Wang, Tangting Chen, Peng Zhang, Li Liu, Chunhong Li, Tao Li, Xiaobin Wang","doi":"10.3892/ijmm.2025.5498","DOIUrl":"10.3892/ijmm.2025.5498","url":null,"abstract":"<p><p>Remimazolam (Rema) is a novel anesthetic that is widely used in anesthesia and sedation in critically ill patients. Notably, Rema exerts effects in patients through activation of the γ‑aminobutyric acid (GABA) receptor. GABA may alleviate myocardial ischemia/reperfusion (I/R) injury; however, the impact of Rema and underlying molecular mechanism in myocardial I/R injury remain to be fully understood. Therefore, the present study aimed to investigate the effects of Rema on cardiac I/R injury and to determine the underlying mechanisms. An acute myocardial I/R model was established by ligating the left anterior descending artery in adult male C57BL/6 mice (8‑10 weeks). Cultured Raw264.7 cells treated with lipopolysaccharide (LPS) were also used to investigate the effect of Rema on macrophages. The results of the present study revealed that Rema improved I/R‑induced cardiac dysfunction by increasing the ejection fraction value and reducing the myocardial infarction area. In addition, Rema also alleviated I/R‑induced cardiac inflammatory cell infiltration based on H&E and immunofluorescence staining. Transmission electron microscopy and ROS measurements showed that Rema improved I/R‑induced mitochondrial structural disruption and oxidative stress in cardiomyocytes. Transcriptomics analysis and reverse transcription‑quantitative PCR revealed that Rema alleviated I/R‑induced release of inflammatory factors and cytokines by inhibiting the expression of IL‑1β, IL‑6, C‑C chemokine receptor 2 and C‑X‑C motif chemokine ligand 5. Rema also inhibited I/R‑induced CD68+ cell proliferation, IL‑1β release, and NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and IL‑1β expression. The results of <i>in vitro</i> assays revealed that Rema inhibited LPS‑induced increases in IL‑1β, IL‑6 and TNF‑α expression and release in cultured RAW264.7 macrophages. In conclusion, the present study revealed that Rema may alleviate I/R‑induced cardiac dysfunction and myocardial injury by inhibiting oxidative stress and inflammatory responses via the NLRP3/IL‑1β pathway.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The off‑target effect of loratadine triggers autophagy‑mediated apoptosis in lung adenocarcinoma cells by deactivating JNK, p38, and STAT3 signaling through both PP2A‑dependent and independent pathways.","authors":"Ming-Hsien Chien, Wen-Yueh Hung, Tsung-Ching Lai, Ching Han Tsai, Kai-Ling Lee, Feng-Koo Hsieh, Wei-Jiunn Lee, Jer-Hwa Chang","doi":"10.3892/ijmm.2025.5495","DOIUrl":"10.3892/ijmm.2025.5495","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a typical inflammation‑associated cancer, and anti‑inflammatory medications can be valuable in cancer therapy. Loratadine, a histamine receptor H1 (HRH1) antagonist, shows both anti‑inflammatory and anticancer properties. The present study aimed to evaluate impacts of loratadine on LUAD cells as well as in a LUAD xenograft mouse model, and explore underlying mechanisms. Mechanistic investigations were conducted through using western blotting, flow cytometry, immunohistochemistry, acridine orange staining, TUNEL assays, and <i>in silico</i> analyses of loratadine‑modulated genes in LUAD specimens. It was observed that loratadine inhibited LUAD cell proliferation and colony formation by inducing autophagy‑mediated apoptotic cell death independently of HRH1. In a LUAD xenograft model, loratadine decreased tumor proliferation and angiogenesis while enhancing autophagy and apoptosis. Mechanistically, loratadine induced protein phosphatase 2A (PP2A) activation to deactivate c‑Jun N‑terminal kinase (JNK)1/2 and p38 in H23 and PC9 LUAD cells. Additionally, loratadine inhibited signal transducer and activator of transcription 3 (STAT3) activation via a PP2A‑independent pathway. Furthermore, the combination of loratadine with inhibitors for JNK, p38 and STAT3 all enhanced proliferation inhibition of loratadine alone in both cell lines. In the clinic, patients with LUAD expressing high PP2A had favorable prognoses. The present study suggests that loratadine can be used as a PP2A activator for LUAD treatment, and the combination of repurposing loratadine with inhibitors of STAT3, JNK and p38 would be an effectively strategy for inhibiting LUAD growth.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11819771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of autophagy in fibrosis: Mechanisms, progression and therapeutic potential (Review).","authors":"Yongxin Chen, Zhuanghui Wang, Qinghong Ma, Chao Sun","doi":"10.3892/ijmm.2025.5502","DOIUrl":"10.3892/ijmm.2025.5502","url":null,"abstract":"<p><p>Various forms of tissue damage can lead to fibrosis, an abnormal reparative reaction. In the industrialized countries, 45% of deaths are attributable to fibrotic disorders. Autophagy is a highly preserved process. Lysosomes break down organelles and cytoplasmic components during autophagy. The cytoplasm is cleared of pathogens and dysfunctional organelles, and its constituent components are recycled. With the growing body of research on autophagy, it is becoming clear that autophagy and its associated mechanisms may have a role in the development of numerous fibrotic disorders. However, a comprehensive understanding of autophagy in fibrosis is still lacking and the progression of fibrotic disease has not yet been thoroughly investigated in relation to autophagy‑associated processes. The present review focused on the latest findings and most comprehensive understanding of macrophage autophagy, endoplasmic reticulum stress‑mediated autophagy and autophagy‑mediated endothelial‑to‑mesenchymal transition in the initiation, progression and treatment of fibrosis. The article also discusses treatment strategies for fibrotic diseases and highlights recent developments in autophagy‑targeted therapies.</p>","PeriodicalId":14086,"journal":{"name":"International journal of molecular medicine","volume":"55 4","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}