Biochimica et biophysica acta. Molecular basis of disease最新文献

{"title":"Hypoxic stress promotes astrocyte infiltration-like growth via HIF-1α/GDNF/LOXL2 axis","authors":"Zimu Li ,&nbsp;Shun Xi ,&nbsp;Ziqi Zhang ,&nbsp;Xugang Kan ,&nbsp;Yang Zhang ,&nbsp;Miaomiao Wang ,&nbsp;Yudong Wang ,&nbsp;Yefeng Shi ,&nbsp;Haoyue Xu ,&nbsp;Baole Zhang","doi":"10.1016/j.bbadis.2025.167702","DOIUrl":"10.1016/j.bbadis.2025.167702","url":null,"abstract":"<div><div>Elevated levels of glial cell line-derived neurotrophic factor (GDNF) are implicated in the transformation of astrocytes into astrogliomas, but the underlying mechanisms are not fully understood. In this study, we found that hypoxia led to a significant increase in GDNF expression in primary rat astrocytes from various brain regions, including the cortex, hippocampus, and corpus callosum. This was accompanied by the activation of astrocytes, particularly those of the A2 subtype, and a concurrent increase in hypoxia-inducible factor 1-alpha (HIF-1α) expression. The elevated levels of HIF-1α enhanced its binding to the GDNF promoter, resulting in increased GDNF expression. Interestingly, this process formed a positive feedback loop, as elevated GDNF further activated HIF-1α in primary rat and human astrocytes. Furthermore, lysyl oxidase-like protein 2 (LOXL2), a novel downstream oncogene of GDNF, showed a significant increase following hypoxia treatment and exhibited a positive correlation with GDNF expression. Inhibiting GDNF signaling effectively suppressed this expression. Hypoxia-induced GDNF also increased the phosphorylation of ERK, P38, and CREB through the classical GDNF receptors, GFRα1 and RET. This led to increased binding of phosphorylated CREB to the LOXL2 promoter, resulting in enhanced LOXL2 expression. Consequently, rat astrocytes under hypoxic stress exhibited increased cell viability, migration, and epithelial-mesenchymal transition, which were mitigated by inhibiting GDNF signaling or silencing LOXL2. This phenomenon was also observed in C6 cells. Our findings suggest that hypoxia induces astrocyte activation and upregulates LOXL2 expression through the HIF-1α/GDNF/P-CREB signaling axis, facilitating the infiltration-like growth of astrocytes and the infiltrative growth of C6 astroglioma cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167702"},"PeriodicalIF":4.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibroblast-specific MyD88-dependent signaling aggravates inflammation and cardiac dysfunction in the MI heart","authors":"Prachi Umbarkar,&nbsp;Sultan Tousif,&nbsp;Ashish Jaiswal,&nbsp;Arvind Singh Bhati,&nbsp;Angelica Toro Cora,&nbsp;Rohan Sethi,&nbsp;Qinkun Zhang,&nbsp;Hind Lal","doi":"10.1016/j.bbadis.2025.167703","DOIUrl":"10.1016/j.bbadis.2025.167703","url":null,"abstract":"<div><h3>Background</h3><div>Excessive fibrosis and chronic inflammation are vital to adverse cardiac remodeling of the MI heart. The crosstalk of fibroblasts (FBs) (primary drivers of fibrosis) and immune cells (that govern inflammation) is critical for the repair and remodeling of the injured heart. However, the molecular mechanisms through which FBs communicate with immune cells are poorly understood. In the MI heart, substantial cardiac cell damage releases alarmins, which trigger an immune response through the TLR/MyD88 pathway. The role of MyD88-dependent signaling is well characterized in immune cell biology. However, the role of FB-derived MyD88 signaling in MI heart injury is unknown.</div></div><div><h3>Objective</h3><div>To define the role of FB-MyD88 in MI pathology.</div></div><div><h3>Methods and results</h3><div>MyD88 was deleted from fibroblasts or myofibroblasts with tamoxifen-inducible Tcf21- or Postn- promoter-driven Cre recombinase. Control and MyD88 KO mice were subjected to permanent LAD ligation (MI injury), and cardiac parameters were evaluated. Additionally, co-culture experiments and chemokine profiling were conducted to identify mechanisms facilitating FB-immune cell crosstalk. FB-specific MyD88 deletion restricted MI-induced adverse cardiac remodeling and cardiac dysfunction. Surprisingly, FB-specific MyD88 deletion reduced myeloid cell recruitment and molecular markers of chronic inflammation in the KO heart. The mechanistic studies confirmed that MyD88 is required for the activation of NF-κB in FBs. Additionally, co-culture experiments demonstrated that FB-MyD88 facilitates immune cell crosstalk through chemokines and promotes an inflammatory gene program.</div></div><div><h3>Conclusion</h3><div>These findings suggest that FB-MyD88 promotes MI-induced chronic inflammation and cardiac dysfunction. Therefore, targeting MyD88 could serve as a potential therapeutic strategy.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167703"},"PeriodicalIF":4.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amylin is incorporated into extracellular vesicles in an ESCRT-dependent manner and regulates senescence","authors":"S. Iglesias-Fortes ,&nbsp;A.C. Lockwood ,&nbsp;C. González-Blanco ,&nbsp;D. Lozano ,&nbsp;A. García-Aguilar ,&nbsp;O. Palomino ,&nbsp;G. García ,&nbsp;E. Fernández-Millán ,&nbsp;M. Benito ,&nbsp;C. Guillén","doi":"10.1016/j.bbadis.2025.167699","DOIUrl":"10.1016/j.bbadis.2025.167699","url":null,"abstract":"<div><div>Type 2 diabetes mellitus is a disease which initiates with insulin resistance. Then, pancreatic β cells start to counteract this situation by increasing insulin secretion, which is known as pre-diabetic state. Amylin protein or islet amyloid polypeptide (IAPP), has multiple physiological roles such as the regulation of satiety and avoiding gastric emptying. However, amylin is able to aggregate, forming insoluble structures that affects pancreatic β cell survival. Interestingly, not all the amylin from the different species has this aggregate-prone capacity. There are species, which possesses non-amyloidogenic capacity and does not aggregate such as the rodents. However, there are versions of the protein, for instance from humans and primates, which can aggregate. Previously, we observed that small oligomers could be found in extracellular vesicles (EVs). Now, we have used a pancreatic β cell which overexpresses human amylin (hIAPP) (INS1E-hIAPP) and we have explored the capacity of amylin to be incorporated into EVs and how amylin could affect to different essential signaling pathways such as the mammalian target of rapamycin complex 1, endoplasmic-reticulum stress and senescence. Here, we report that amylin can be incorporated into EVs in an endosomal sorting complexes required for transport (ESCRT)-dependent manner. When we treated the cells with the neutral sphingomyelinase inhibitor, GW4869, one of the pathways for EV biogenesis and under high glucose conditions, there was an increased incorporation of soluble amylin into vesicles. Interestingly in this condition, when we isolated the EVs, we clearly observed that the size of the vesicles was higher, compatible with microvesicles (MVs). Resveratrol increased a pro-senescent phenotype but, it was able to revert either the high glucose or GW4869-associated senescent. In summary, these results indicate that amylin can be recruited in an ESCRT-dependent manner into EVs and, resveratrol presents an important role in inducing senescence in INS1E-hIAPP pancreatic β cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 4","pages":"Article 167699"},"PeriodicalIF":4.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programmed cell death protein 5 inhibits hepatocellular carcinoma progression by inducing pyroptosis through regulation of TGF-β/Smad2/3/Snail pathway","authors":"Yiqiao Wang ,&nbsp;Shihao Huang ,&nbsp;Yangbai Cai ,&nbsp;Taicheng Wang ,&nbsp;Hongyan Zhao ,&nbsp;Xianke Lin ,&nbsp;Xueguo Wang ,&nbsp;Peng Li","doi":"10.1016/j.bbadis.2025.167696","DOIUrl":"10.1016/j.bbadis.2025.167696","url":null,"abstract":"<div><h3>Background</h3><div>Programmed cell death protein 5 (PDCD5) is involved in apoptosis and is regarded as a tumor suppressor in various tumors. However, its role and underlying molecular mechanisms in hepatocellular carcinoma (HCC) remain unclear.</div></div><div><h3>Methods</h3><div>PDCD5-overexpressing cell and xenograft tumor models were developed. Cell Counting Kit-8, 5-Ethynyl-2′-deoxyuridine, wound healing, Transwell, flow cytometry, immunohistochemistry, and hematoxylin-eosin staining were employed to explore the effects of PDCD5 on HCC cell behaviors and tumor growth. The enzyme-linked immunosorbent assay and western blot were used to detect pyroptosis-related marker levels. The molecular mechanisms underlying PDCD5's role in HCC were investigated through transcriptome sequencing and coimmunoprecipitation. SRI-011381, a TGF-β signaling activator, was applied to evaluate the impact of PDCD5 in modulating the TGF-β/Smad2/3/Snail pathway.</div></div><div><h3>Results</h3><div>PDCD5 expression was reduced in HCC cells. Overexpression of PDCD5 inhibited HCC cell proliferation, migration, invasion, and xenograft tumor growth. Additionally, PDCD5 overexpression promoted apoptosis and pyroptosis, with corresponding increases in inflammatory factors and Caspase-1, GSDMD, and NLRP3 protein levels. Mechanistically, PDCD5 bound to receptor-regulated Smads (Smad2/3), inhibiting the TGF-β pathway. Treatment with the TGF-β pathway activator SRI-011381 significantly counteracted the inhibitory effects of PDCD5 overexpression on HCC progression.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that PDCD5 impedes the progression of HCC by promoting pyroptosis <em>via</em> regulation of TGF-β/Smad2/3/Snail pathway, which could be a possible therapeutic target for HCC.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167696"},"PeriodicalIF":4.2,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The curious case of mitochondrial sirtuin in rewiring breast cancer metabolism: Mr Hyde or Dr Jekyll?","authors":"Jesline Shaji Tharayil ,&nbsp;Amoolya Kandettu ,&nbsp;Sanjiban Chakrabarty","doi":"10.1016/j.bbadis.2025.167691","DOIUrl":"10.1016/j.bbadis.2025.167691","url":null,"abstract":"<div><div>Mammalian sirtuins are class III histone deacetylases involved in the regulation of multiple biological processes including senescence, DNA repair, apoptosis, proliferation, caloric restriction, and metabolism. Among the mammalian sirtuins, SIRT3, SIRT4, and SIRT5 are localized in the mitochondria and collectively termed the mitochondrial sirtuins. Mitochondrial sirtuins are NAD+-dependent deacetylases that play a central role in cellular metabolism and function as epigenetic regulators by performing post-translational modification of cellular proteins. Several studies have identified the role of mitochondrial sirtuins in age-related pathologies and the rewiring of cancer metabolism. Mitochondrial sirtuins regulate cellular functions by contributing to post-translational modifications, including deacetylation, ADP-ribosylation, demalonylation, and desuccinylation of diverse cellular proteins to maintain cellular homeostasis. Here, we review and discuss the structure and function of the mitochondrial sirtuins and their role as metabolic regulators in breast cancer. Altered breast cancer metabolism may promote tumor progression and has been an essential target for therapy. Further, we discuss the potential role of targeting mitochondrial sirtuin and its impact on breast cancer progression using sirtuin inhibitors and activators as anticancer agents.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167691"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRCC3 aggravates pulpitis by activating the NF-κB signaling pathway in dental pulp cells","authors":"Xinye Zhang ,&nbsp;Lu Zhang ,&nbsp;Linfang Zhou ,&nbsp;Huangheng Tao ,&nbsp;Zhi Chen","doi":"10.1016/j.bbadis.2025.167698","DOIUrl":"10.1016/j.bbadis.2025.167698","url":null,"abstract":"<div><div>BRCA1/BRCA2-containing complex subunit 3 (BRCC3) has been proved to exert pro-inflammatory effect in various inflammatory diseases through different mechanisms, but its involvement in pulpitis remains unclear. This study aims to investigate the regulatory role and mechanisms of BRCC3 in modulating dental pulp cell inflammation and pulpitis progression. The expression of <em>BRCC3</em> was observed to be elevated in human/mouse pulpitis samples and lipopolysaccharide-stimulated human dental pulp cells (hDPCs). Manipulation of <em>BRCC3</em> expression revealed that BRCC3 facilitated the expression of pro-inflammatory cytokines and apoptosis of hDPCs. RNA-sequencing and gene set enrichment analysis were utilized to explore the downstream signaling pathways related to BRCC3 functions. Dual luciferase reporter assay, western blot, and immunofluorescence staining were conducted for further validation. The results demonstrated that BRCC3 expedited IκBα phosphorylation and degradation, as well as p65 phosphorylation and nuclear translocation in hDPCs, ultimately activating the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, conditional knockout of <em>Brcc3</em> in mouse dental pulp cells effectively impeded the expression of IL-6, recruitment of immune cells, and necrosis of inflamed pulp tissue after 1 day and 1 week of pulp exposure. The level of p-p65 in <em>Brcc3</em> conditional knockout mice was lower than the control mice, indicating the inhibition of NF-κB. Taken together, BRCC3 promotes pulpitis by activating the NF-κB signaling pathway in dental pulp cells.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167698"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting GSK3 to attenuate spaceflight-induced SERCA dysfunction: Lessons from hindlimb-suspended mice","authors":"Amélie A.T. Marais,&nbsp;Ryan W. Baranowski,&nbsp;Jessica L. Braun,&nbsp;Briana L. Hockey,&nbsp;Val A. Fajardo","doi":"10.1016/j.bbadis.2025.167694","DOIUrl":"10.1016/j.bbadis.2025.167694","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>In the absence of gravity, muscles become unloaded, reducing their size, strength, and endurance.</div></span></li><li><span>•</span><span><div>Calcium (Ca²⁺) dysregulation due to impairments in sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) function may be one reason for the decline in muscle performance.</div></span></li><li><span>•</span><span><div>Our previous work has shown that genetic reduction of glycogen synthase kinase 3 (GSK3) maintains soleus muscle mass and strength in mice after 7 days of hindlimb suspension.</div></span></li><li><span>•</span><span><div>Here, we tested whether these benefits could be, in part, due to an improvement in SERCA activity.</div></span></li><li><span>•</span><span><div>We show that muscle-specific GSK3 knockdown enhances soleus maximal SERCA activity, SERCA1 protein content, soleus relaxation and soleus muscle endurance.</div></span></li></ul></div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167694"},"PeriodicalIF":4.2,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing and machine learning provide candidate drugs against drug-tolerant persister cells in colorectal cancer","authors":"Yosui Nojima ,&nbsp;Ryoji Yao ,&nbsp;Takashi Suzuki","doi":"10.1016/j.bbadis.2025.167693","DOIUrl":"10.1016/j.bbadis.2025.167693","url":null,"abstract":"<div><div>Drug resistance often stems from drug-tolerant persister (DTP) cells in cancer. These cells arise from various lineages and exhibit complex dynamics. However, effectively targeting DTP cells remains challenging. We used single-cell RNA sequencing (scRNA-Seq) data and machine learning (ML) models to identify DTP cells in patient-derived organoids (PDOs) and computationally screened candidate drugs targeting these cells in familial adenomatous polyposis (FAP), associated with a high risk of colorectal cancer. Three PDOs (benign and malignant tumor organoids and a normal organoid) were evaluated using scRNA-Seq. ML models constructed based on public scRNA-Seq data classified DTP versus non-DTP cells. Candidate drugs for DTP cells in a malignant tumor organoid were identified from public drug sensitivity data. From FAP scRNA-Seq data, a specific TC1 cell cluster in tumor organoids was identified. The ML model identified up to 36 % of TC1 cells as DTP cells, a higher proportion than those for other clusters. A viability assay using a malignant tumor organoid demonstrated that YM-155 and THZ2 exert synergistic effects with trametinib. The constructed ML model is effective for DTP cell identification based on scRNA-Seq data for FAP and provides candidate treatments. This approach may improve DTP cell targeting in the treatment of colorectal and other cancers.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167693"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Doxorubicin-induced phosphorylation of lamin A/C enhances DNMT1 and activates cardiomyocyte death via suppressing GATA-4 and Bcl-xL in rat heart","authors":"Vikas Tiwari ,&nbsp;Sanjay Salgar ,&nbsp;Sachin B. Jorvekar ,&nbsp;Bhagyashri Manoj Kumbhar ,&nbsp;Sudheer K. Arava ,&nbsp;Roshan M. Borkar ,&nbsp;Sanjay K. Banerjee","doi":"10.1016/j.bbadis.2025.167692","DOIUrl":"10.1016/j.bbadis.2025.167692","url":null,"abstract":"<div><div>Cardiotoxic effect of Doxorubicin (Dox) limits its clinical application. Previously, we reported that Dox induces phosphorylation of lamin A/C (pS22 lamin A/C), increased nuclear size, damage to the nuclear membrane, and cell death. However, the activation of signalling pathway during this event remains elusive, and it is unclear whether increased phospho-lamin A/C activates the cell death pathway in heart. Here, we demonstrated that Dox-induced lamin A/C phosphorylation causes apoptotic cell death. Increased levels of reactive oxygen species (ROS), DNA methylation and apoptosis markers (Bax, Bid, caspase 3 and caspase 9) were observed in Dox-exposed H9c2 cells. Nuclear membrane damage due to increased pS22 lamin A/C causes increased DNMT1 and DNA methylation followed by reduced expression of GATA-4 and Bcl-xL in Dox-treated H9c2 cells and rat hearts. Further, increased mRNA expression of DNMT1 and reduced expression of GATA-4 and Bcl-xL was observed in H9c2 cells after knocking down of lamin A/C expression. Previously, we reported that <em>N</em>-acetylcysteine improves lamin A/C levels and maintain nuclear membrane integrity. Similarly, in this study Astaxanthin (Ast), a membrane-specific antioxidant, reduces the expression of DNMT1 and phospho-lamin A/C levels; increases mRNA expression of GATA-4 and Bcl-xL; reduces ROS levels and DNA leakage in Dox-treated H9c2 cells and rat hearts. Ast also improves the cardiac structure and function in Dox-treated rats. In conclusion, Dox exposure in cardiomyoblasts and hearts causes cell death by increasing the pS22 lamin A/C, DNA methylation and reducing the expression GATA-4 and Bcl-xL. This study provides a novel pathway for Dox-induced cardiotoxicity and a possible therapeutic approach to reduce it.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167692"},"PeriodicalIF":4.2,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic reticulum stress in liver fibrosis: Mechanisms and therapeutic potential","authors":"Tiantian Wang ,&nbsp;Guoqing Xia ,&nbsp;Xue Li,&nbsp;Mingxu Gong,&nbsp;Xiongwen Lv","doi":"10.1016/j.bbadis.2025.167695","DOIUrl":"10.1016/j.bbadis.2025.167695","url":null,"abstract":"<div><div>This paper reviews the important role of endoplasmic reticulum stress in the patho mechanism of liver fibrosis and its potential as a potential target for the treatment of liver fibrosis. Liver fibrosis is the result of sustained inflammation and injury to the liver due to a variety of factors, triggering excessive deposition of extracellular matrix and fibrous scar formation, which in turn leads to loss of liver function and a variety of related complications. Endoplasmic reticulum stress is one of the characteristics of chronic liver disease and is closely related to the pathological process of chronic liver disease, including alcohol-related liver disease, viral hepatitis, and liver fibrosis. The unfolded protein response is one of the important response mechanisms to endoplasmic reticulum stress. It is associated with several pathological aspects of liver fibrosis and the maintenance of endoplasmic reticulum homeostasis. Interventions targeting endoplasmic reticulum stress for the treatment of liver fibrosis have potential research and application value. An in-depth understanding of the biological basis of endoplasmic reticulum stress is also needed in the treatment of liver fibrosis, as well as the development of more effective drugs and interventions to accurately regulate the endoplasmic reticulum signaling network, to achieve the restoration and maintenance of endoplasmic reticulum homeostasis at the cellular and organ levels, and to further promote the reversal of the pathological process of liver fibrosis.</div></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":"1871 3","pages":"Article 167695"},"PeriodicalIF":4.2,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}