{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:41:28Z","timestamp":1789501288743,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T00:00:00Z","timestamp":1528675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31540094, 81600481"],"award-info":[{"award-number":["31540094, 81600481"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver fibrosis is the common pathological process characterized by activation of hepatic stellate cells (HSCs) and overproduction of extracellular matrix (ECM). Caveolin-1 (Cav1), the principal component of caveolae, is regarded as an important inhibitor of multiple signaling molecules including transforming growth factor \u03b21(TGF-\u03b21) signaling. To evaluate the role of Cav1 in liver fibrosis, Cav1 deficient (Cav1\u2212\/\u2212) and wild type (WT) mice were subjected to liver fibrosis induced by carbon tetrachloride (CCl4). Results indicated no significant difference between Cav1\u2212\/\u2212 and WT mice in inflammation or collagen content before CCl4 treatment. After CCl4 administration, Cav1\u2212\/\u2212 mice showed enhanced TGF-\u03b21 signaling, as reflected by a significantly greater amount of phosphorylation of Smad2 and collagen deposition in livers over WT animals. Qualitative and quantitative analysis indicated that inflammatory injury to the liver was markedly aggravated, accompanied by increased degeneration and necrosis of hepatocytes, higher alanine aminotransferase (ALT)\/aspartate aminotransferase (AST), TGF-\u03b1 and IL-1\u03b2 levels in Cav1\u2212\/\u2212 animals. The mRNA and protein levels of \u03b1-smooth muscle actin (\u03b1-SMA), Collagen \u03b11(I), and Collagen \u03b11(III) were further enhanced in Cav1\u2212\/\u2212 animals. We also observed a significant decrease in collagen content in Cav1\u2212\/\u2212 and WT animals administrated with Cav1 scaffolding domain peptides (CSD). In vitro study indicated that phosphorylation of Smad2 was inhibited after CSD treatment, accompanied by decreased protein levels of \u03b1-SMA, Collagen \u03b11(I), and Collagen \u03b11(III) in HSCs. We conclude that Cav1 is an important inhibitor of TGF-\u03b21\/Smad signaling in HSCs activation and collagen production, which might make it a promising target for therapy of liver fibrosis.<\/jats:p>","DOI":"10.3390\/ijms19061729","type":"journal-article","created":{"date-parts":[[2018,6,11]],"date-time":"2018-06-11T11:01:01Z","timestamp":1528714861000},"page":"1729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Caveolin-1 Scaffolding Domain Peptides Alleviate Liver Fibrosis by Inhibiting TGF-\u03b21\/Smad Signaling in Mice"],"prefix":"10.3390","volume":"19","author":[{"given":"Jing","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"167sr1","DOI":"10.1126\/scitranslmed.3004700","article-title":"Therapy for fibrotic diseases: Nearing the starting line","volume":"5","author":"Friedman","year":"2013","journal-title":"Sci. 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