{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:27:36Z","timestamp":1791023256441,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":3956,"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":[[2004,11]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Activation of hepatic stellate cells (HSCs) and other resident mesenchymal cells into myofibroblasts expressing alpha smooth muscle actin (\u03b1SMA) and collagen I is a key event in liver fibrogenesis. However, the temporal expression profiles of \u03b1SMA and collagen I genes in these cells is unknown. To address this question, we studied \u03b1SMA and collagen \u03b11(I) transcriptional patterns in primary cultures of HSCs, and additionally, in an <jats:italic toggle=\"yes\">in vivo<\/jats:italic> model of secondary biliary fibrosis using transgenic mice that express the <jats:italic toggle=\"yes\">Discomsoma sp.<\/jats:italic> red fluorescent protein (RFP) and the enhanced green fluorescent protein (EGFP) reporter genes under direction of the mouse \u03b1SMA and collagen \u03b11(I) promoter\/enhancers, respectively. The \u03b1SMA-RFP mice were crossed with collagen-EGFP mice to generate double transgenic mice. Reporter gene expression in cultured HSCs demonstrated that both transgenes were induced at day 3 with continued expression through day 14. Interestingly, \u03b1SMA and collagen \u03b11(I) transgenes were not coexpressed in all cells. Flow cytometry analysis showed three different patterns of gene expression: \u03b1SMA-RFP positive cells, collagen-EGFP positive cells, and cells expressing both transgenes. \u03b1SMA-only and \u03b1SMA\/collagen expressing cells showed higher expression levels of synaptophysin, reelin, MMP13, TIMP1, and ICAM-1 compared to collagen-only expressing cells, as assessed by real-time PCR. Following bile duct ligation, \u03b1SMA and collagen \u03b11(I) transgenes were differentially expressed by peribiliary, parenchymal and vascular fibrogenic cells. Peribiliary cells preferentially expressed collagen \u03b11(I), while parenchymal myofibroblasts expressed both \u03b1SMA and collagen \u03b11(I). <jats:underline>In conclusion<\/jats:underline>, these data demonstrate heterogeneity of gene expression in myofibroblastic cells during active fibrogenesis. These reporter mice provide a useful tool to further characterize fibrogenic cell types and to evaluate antifibrotic drugs. (Hepatology 2004.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20427","type":"journal-article","created":{"date-parts":[[2004,9,23]],"date-time":"2004-09-23T13:01:17Z","timestamp":1095944477000},"page":"1151-1159","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":216,"title":["A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations"],"prefix":"10.1097","volume":"40","author":[{"given":"Scott T.","family":"Magness","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Bataller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Brenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"Suppl 1","key":"R1-17-20241201","first-page":"S38S53","article-title":"Liver Fibrosis From bench to bedside.","volume":"38","year":"2003","journal-title":"J Hepatol"},{"key":"R2-17-20241201","doi-asserted-by":"crossref","first-page":"4374351","DOI":"10.1055\/s-2001-17558","article-title":"Hepatic Stellate cells as a target for the treatment of liver fibrosis.","volume":"21","author":"Bataller","year":"2001","journal-title":"Semin Liver Dis"},{"key":"R3-17-20241201","doi-asserted-by":"crossref","first-page":"450459","DOI":"10.1172\/JCI113618","article-title":"Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer.","volume":"82","author":"Maher","year":"1988","journal-title":"J Clin Invest"},{"key":"R4-17-20241201","doi-asserted-by":"crossref","first-page":"175184","DOI":"10.1016\/0016-5085(90)91307-R","article-title":"Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis.","volume":"98","author":"Milani","year":"1990","journal-title":"Gastroenterology"},{"key":"R5-17-20241201","doi-asserted-by":"crossref","first-page":"d808d826","DOI":"10.2741\/reeves","article-title":"Activation of hepatic stellate cellsa key issue in liver fibrosis.","volume":"7","author":"Reeves","year":"2002","journal-title":"Front Biosci"},{"key":"R6-17-20241201","first-page":"193203","article-title":"Rat Hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture.","volume":"24","author":"Rockey","year":"1992","journal-title":"J Submicrosc Cytol Pathol"},{"key":"R7-17-20241201","doi-asserted-by":"crossref","first-page":"d496d503","DOI":"10.2741\/kinnman","article-title":"Peribiliary myofibroblasts in biliary type liver fibrosis.","volume":"7","author":"Kinnman","year":"2002","journal-title":"Front Biosci"},{"key":"R8-17-20241201","doi-asserted-by":"crossref","first-page":"12051221","DOI":"10.1016\/S0016-5085(99)70407-5","article-title":"Saile, B, Grundmann, A, Neubauer, K, Piscaglia, F, et al. 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