Preservation of basal AcSDKP attenuates carbon tetrachloride-induced fibrosis in the rat liver

Journal of Hepatology
Yuan-Wen ChenDing-Guo Li

Abstract

N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous tetrapeptide which has antifibrogenic effects at physiological concentrations in various tissues. AcSDKP is produced locally in the liver, however, little is known about its biological effect in this organ. We hypothesize that basal levels of endogenous AcSDKP decrease during the development of liver fibrosis and preservation of basal AcSDKP attenuates liver fibrosis. Endogenous levels of AcSDKP in the liver were measured by enzyme immunoassay after 2, 6, and 10 weeks of carbon tetrachloride (CCl(4))-induced liver fibrosis in rats. Subcutaneous osmotic pump infusion of vehicle or AcSDKP (800 microg/kg/day) was administered to CCl(4)-treated rats for 8 weeks to study the effect of exogenous AcSDKP on liver fibrosis. The effect of AcSDKP on profibrogenic properties of hepatic stellate cells was studied in vitro. Endogenous AcSDKP was significantly decreased in the liver of CCl(4)-treated rats. Chronic AcSDKP infusion preserved basal levels of AcSDKP and reduced liver injury, inflammation, fibrosis, and profibrogenic transforming growth factor-beta signaling. This was demonstrated by decreased aminotransferase serum levels, CD45 positive cells, collagen accumulation, ...Continue Reading

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Citations

Jan 29, 2013·Clinical and Experimental Pharmacology & Physiology·Ross G DouglasEdward D Sturrock
May 27, 2015·International Journal of Molecular Sciences·Jieun Kim, Youngmi Jung
Jan 19, 2016·Frontiers in Pharmacology·Ralf Weiskirchen
Aug 28, 2012·International Immunopharmacology·Hechang TanNiansheng Yang
Aug 11, 2012·Journal of the American Society of Nephrology : JASN·Hirokazu Okada
Mar 30, 2017·Experimental and Therapeutic Medicine·Da ZhouJian-Gao Fan
Mar 11, 2016·American Journal of Physiology. Renal Physiology·Nitin KumarOscar A Carretero

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