{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T01:33:26Z","timestamp":1772156006180,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>Congenital hepatic fibrosis (CHF) is an important cause of morbidity and mortality in patients with autosomal recessive polycystic kidney disease (ARPKD). The pathogenesis of CHF remains undefined. Several recent studies suggest that the renin\u2010angiotensin system (RAS) is an important mediator of progressive hepatic fibrosis through activation of profibrotic mediators, such as transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2). RAS activation has not previously been studied in patients with CHF or in animal models. The aim of the present study was to characterize RAS expression during the course of CHF in the PCK rat.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods:<\/jats:title>\n                    <jats:p>\n                      Studies were conducted in the PCK rat, an orthologous ARPKD\/CHF model, and age\u2010matched normal control Sprague\u2010Dawley rats. Expression of the RAS components, renin, angiotensinogen, angiotensin\u2010converting enzyme (ACE), and angiotensin II type 1 receptor (AT\n                      <jats:sub>1<\/jats:sub>\n                      R), as well as the profibrotic mediator TGF\u2010\u03b2, was examined in cystic PCK and control rat livers at 2, 4, and 6 months of age by quantitative real\u2010time polymerase chain rection (qRT\u2010PCR). Angiotensin II (ANG II) was examined by immunohistochemistry (IHC). Fibrosis was assessed by IHC using reticulin staining and Masson trichrome. Collagen content was determined by hydroxyproline analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Progressive fibrosis and increased hepatic collagen content occurred in PCK rats with age. In 4\u2010 and 6\u2010month\u2010old PCK rat livers, ACE gene expression was markedly increased, 8\u2010 and 17\u2010fold, respectively, compared with age\u2010matched control livers. Expression of the other RAS components, renin, angiotensinogen, and AT\n                      <jats:sub>1<\/jats:sub>\n                      R were not significantly different. IHC demonstrated prominent ANG II protein expression in periportal regions in PCK rats. In contrast, no expression was noted in control livers. TGF\u2010\u03b2 expression was also increased in PCK rat livers with progressive disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      The present study demonstrates, for the first time, RAS upregulation in an orthologous rat ARPKD\/CHF model. Increases in ACE and ANG II, as well as the downstream target, the profibrotic mediator TGF\u2010\u03b2, suggest that RAS activation may be an important mediator of CHF disease progression. The findings also suggest that treatment with RAS inhibitors, specifically ACE inhibitors or AT\n                      <jats:sub>1<\/jats:sub>\n                      R blockers, could be therapeutic in slowing disease progression in CHF.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/mpg.0b013e3181cc80e4","type":"journal-article","created":{"date-parts":[[2010,4,15]],"date-time":"2010-04-15T06:59:40Z","timestamp":1271314780000},"page":"639-644","source":"Crossref","is-referenced-by-count":18,"title":["Renin\u2010angiotensin System Activation in Congenital Hepatic Fibrosis in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease"],"prefix":"10.1002","volume":"50","author":[{"given":"Miwa","family":"Goto","sequence":"first","affiliation":[{"name":"Department of Research MetroHealth Medical Center Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nita","family":"Hoxha","sequence":"additional","affiliation":[{"name":"Department of Research MetroHealth Medical Center Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rania","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Research MetroHealth Medical Center Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Wen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition the Children's Hospital of Philadelphia Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca G","family":"Wells","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology and Laboratory Medicine University of Pennsylvania School of Medicine Philadelphia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine MacRae","family":"Dell","sequence":"additional","affiliation":[{"name":"Department of Research MetroHealth Medical Center Case Western Reserve University Cleveland OH USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,6]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.111.5.1072"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8553(03)00054-2"},{"key":"e_1_2_6_4_1","unstructured":"DellKM AvnerED.Autosomal recessive polycystic kidney disease. GeneClinics: Clinical Genetic Information Resource [database online]. University of Washington Seattle.http:\/\/www.geneclinics.org. Published July 2001. Accessed March 29 2010."},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2005.00342.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3046.2003.00094.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-6143.2002.20412.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng833"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20665"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24282"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.36561"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.279.5.G845"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00473.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64116-8"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.12.039"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00036.2005"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18212"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04663.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00281.2004"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000042703.39845.B4"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.1.31"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2004001000002"},{"key":"e_1_2_6_23_1","first-page":"135","article-title":"Hepatic fibrosis and cirrhosis: the (myo)fibroblastic cell subpopulations involved","volume":"38","author":"Guyot C","year":"2006","journal-title":"Int J Biochem Cell Biol"}],"container-title":["Journal of Pediatric Gastroenterology and Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MPG.0b013e3181cc80e4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T08:35:45Z","timestamp":1705566945000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MPG.0b013e3181cc80e4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,6]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2010,6]]}},"alternative-id":["10.1097\/MPG.0b013e3181cc80e4"],"URL":"https:\/\/doi.org\/10.1097\/mpg.0b013e3181cc80e4","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3868956.3606054","asserted-by":"object"}]},"ISSN":["0277-2116","1536-4801"],"issn-type":[{"value":"0277-2116","type":"print"},{"value":"1536-4801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,6]]}}}