{"title":"REDD1减轻胆汁淤积性肝纤维化,抑制PI3K/AKT/mTOR通路。","authors":"Xiaonan Li, Xin Liu, Xinrui Shi, Zixu Li, Qizhi Shuai, Tingjuan Huang, Yun Liu, Junjie Ren","doi":"10.3389/fmed.2025.1628260","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Liver fibrosis is reversible. Cholestasis is an important factor causing liver fibrosis. However, there are currently no effective anti-fibrotic drugs for cholestatic liver fibrosis in clinical practice.</p><p><strong>Methods: </strong>mRNA sequencing was performed using mouse bile duct ligation (BDL) of liver tissue, and RT-qPCR was used to screen for the target gene REDD1. Immunohistochemistry was used to detect the expression of REDD1, CD68, α-SMA, and PI3K/AKT/mTOR signaling pathways in primary biliary cholangitis (PBC) patient liver tissue. Subsequently, adenovirus mediated REDD1 was transfected into mouse liver tissue via tail vein to evaluate its therapeutic effect.</p><p><strong>Results: </strong>RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with α-SMA and CD68 in PBC patients, suggesting its involvement in fibrogenesis. However, REDD1 overexpression ameliorated BDL-induced liver injury, reduced serum ALT/AST levels, and decreased collagen deposition, as evidenced by histological and molecular analyses (α-SMA and collagen I), indicating that REDD1 exhibited compensatory elevation in liver fibrosis. Additionally, PI3K/AKT/mTOR pathway was involved in the improvement of liver fibrosis by REDD1.</p><p><strong>Conclusions: </strong>These findings highlight REDD1 as a potential therapeutic target for liver fibrosis, acting probably through modulation of the PI3K/AKT/mTOR pathway to mitigate fibrotic processes.</p>","PeriodicalId":12488,"journal":{"name":"Frontiers in Medicine","volume":"12 ","pages":"1628260"},"PeriodicalIF":3.1000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504318/pdf/","citationCount":"0","resultStr":"{\"title\":\"REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway.\",\"authors\":\"Xiaonan Li, Xin Liu, Xinrui Shi, Zixu Li, Qizhi Shuai, Tingjuan Huang, Yun Liu, Junjie Ren\",\"doi\":\"10.3389/fmed.2025.1628260\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Liver fibrosis is reversible. Cholestasis is an important factor causing liver fibrosis. However, there are currently no effective anti-fibrotic drugs for cholestatic liver fibrosis in clinical practice.</p><p><strong>Methods: </strong>mRNA sequencing was performed using mouse bile duct ligation (BDL) of liver tissue, and RT-qPCR was used to screen for the target gene REDD1. Immunohistochemistry was used to detect the expression of REDD1, CD68, α-SMA, and PI3K/AKT/mTOR signaling pathways in primary biliary cholangitis (PBC) patient liver tissue. Subsequently, adenovirus mediated REDD1 was transfected into mouse liver tissue via tail vein to evaluate its therapeutic effect.</p><p><strong>Results: </strong>RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with α-SMA and CD68 in PBC patients, suggesting its involvement in fibrogenesis. However, REDD1 overexpression ameliorated BDL-induced liver injury, reduced serum ALT/AST levels, and decreased collagen deposition, as evidenced by histological and molecular analyses (α-SMA and collagen I), indicating that REDD1 exhibited compensatory elevation in liver fibrosis. Additionally, PI3K/AKT/mTOR pathway was involved in the improvement of liver fibrosis by REDD1.</p><p><strong>Conclusions: </strong>These findings highlight REDD1 as a potential therapeutic target for liver fibrosis, acting probably through modulation of the PI3K/AKT/mTOR pathway to mitigate fibrotic processes.</p>\",\"PeriodicalId\":12488,\"journal\":{\"name\":\"Frontiers in Medicine\",\"volume\":\"12 \",\"pages\":\"1628260\"},\"PeriodicalIF\":3.1000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12504318/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fmed.2025.1628260\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fmed.2025.1628260","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
REDD1 attenuates cholestatic liver fibrosis and suppresses PI3K/AKT/mTOR pathway.
Introduction: Liver fibrosis is reversible. Cholestasis is an important factor causing liver fibrosis. However, there are currently no effective anti-fibrotic drugs for cholestatic liver fibrosis in clinical practice.
Methods: mRNA sequencing was performed using mouse bile duct ligation (BDL) of liver tissue, and RT-qPCR was used to screen for the target gene REDD1. Immunohistochemistry was used to detect the expression of REDD1, CD68, α-SMA, and PI3K/AKT/mTOR signaling pathways in primary biliary cholangitis (PBC) patient liver tissue. Subsequently, adenovirus mediated REDD1 was transfected into mouse liver tissue via tail vein to evaluate its therapeutic effect.
Results: RNA sequencing revealed REDD1 was significantly upregulated in BDL-induced fibrotic liver tissue. REDD1 expression correlated positively with α-SMA and CD68 in PBC patients, suggesting its involvement in fibrogenesis. However, REDD1 overexpression ameliorated BDL-induced liver injury, reduced serum ALT/AST levels, and decreased collagen deposition, as evidenced by histological and molecular analyses (α-SMA and collagen I), indicating that REDD1 exhibited compensatory elevation in liver fibrosis. Additionally, PI3K/AKT/mTOR pathway was involved in the improvement of liver fibrosis by REDD1.
Conclusions: These findings highlight REDD1 as a potential therapeutic target for liver fibrosis, acting probably through modulation of the PI3K/AKT/mTOR pathway to mitigate fibrotic processes.
期刊介绍:
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate
- the use of patient-reported outcomes under real world conditions
- the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines
- the scientific bases for guidelines and decisions from regulatory authorities
- access to medicinal products and medical devices worldwide
- addressing the grand health challenges around the world