{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:51:43Z","timestamp":1791057103084,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2344,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,4]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Cathepsins have been best characterized in tumorigenesis and cell death and implicated in liver fibrosis; however, whether cathepsins directly regulate hepatic stellate cell (HSC) activation and proliferation, hence modulating their fibrogenic potential, is largely unknown. Here, we show that expression of cathepsin B (CtsB) and cathepsin D (CtsD) is negligible in quiescent HSCs but parallels the increase of \u03b1-smooth muscle actin and transforming growth factor-\u03b2 during\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      mouse HSC activation. Both cathepsins are necessary for HSC transdifferentiation into myofibroblasts, because their silencing or inhibition decreased HSC proliferation and the expression of phenotypic markers of HSC activation, with similar results observed with the human HSC cell line LX2. CtsB inhibition blunted AKT phosphorylation in activated HSCs in response to platelet-derived growth factor. Moreover, during\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      liver fibrogenesis caused by CCl\n                      <jats:sub>4<\/jats:sub>\n                      administration, CtsB expression increased in HSCs but not in hepatocytes, and its inactivation mitigated CCl\n                      <jats:sub>4<\/jats:sub>\n                      -induced inflammation, HSC activation, and collagen deposition.\n                      <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                      These findings support a critical role for cathepsins in HSC activation, suggesting that the antagonism of cathepsins in HSCs may be of relevance for the treatment of liver fibrosis. (Hepatology 2009.)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.22753","type":"journal-article","created":{"date-parts":[[2008,11,25]],"date-time":"2008-11-25T13:55:06Z","timestamp":1227621306000},"page":"1297-1307","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":90,"title":["Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential #"],"prefix":"10.1097","volume":"49","author":[{"given":"Anna","family":"Moles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Tarrats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 C.","family":"Fern\u00e1ndez-Checa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Mar\u00ed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-27-20241201","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver.","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol Rev"},{"key":"R2-27-20241201","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cca.2005.06.014","article-title":"Mechanisms of liver fibrosis.","volume":"364","author":"Tsukada","year":"2006","journal-title":"Clin Chim Acta"},{"key":"R3-27-20241201","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1172\/JCI30542","article-title":"Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ.","volume":"117","author":"Iredale","year":"2007","journal-title":"J Clin Invest"},{"key":"R4-27-20241201","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis.","volume":"115","author":"Bataller","year":"2005","journal-title":"J Clin Invest"},{"key":"R5-27-20241201","doi-asserted-by":"crossref","first-page":"S84","DOI":"10.1111\/j.1440-1746.2006.04584.x","article-title":"Hepatic stellate cells and the reversal of fibrosis.","volume":"21","author":"Kisseleva","year":"2006","journal-title":"J Gastroenterol Hepatol"},{"key":"R6-27-20241201","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1172\/JCI115561","article-title":"Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells. 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