title: HS-173, a novel PI3K inhibitor, attenuates the activation of hepatic stellate cells in liver fibrosis.
abstract: Hepatic stellate cells (HSCs) are the primary source of matrix components in liver disease such as fibrosis. Phosphatidylinositol 3-kinase (PI3K) signaling in HSCs has been shown to induce fibrogenesis. In this study, we evaluated the anti-fibrotic activity of a novel imidazopyridine analogue (HS-173) in human HSCs as well as mouse liver fibrosis. HS-173 strongly suppressed the growth and proliferation of HSCs and induced the arrest at the G2/M phase and apoptosis in HSCs. Furthermore, it reduced the expression of extracellular matrix components such as collagen type I, which was confirmed by an in vivo study. We also observed that HS-173 blocked the PI3K/Akt signaling pathway in vitro and in vivo. Taken together, HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signaling. Therefore, we suggest that this compound may be an effective therapeutic agent for ameliorating liver fibrosis through the inhibition of PI3K signaling.
authors: 1] Department of Medicine, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 400-712, Republic of Korea [2].
authors: Mi Kwon
authors: MK
authors: Son
authors: Ye-Lim
authors: YL
authors: Ryu
authors: Kyung Hee
authors: KH
authors: Jung
authors: Hyunseung
authors: H
authors: Lee
authors: Hee Seung
authors: HS
authors: Lee
authors: Hong Hua
authors: HH
authors: Yan
authors: Heon Joo
authors: HJ
authors: Park
authors: Ji-Kan
authors: JK
authors: Ryu
authors: Jun-Kyu
authors: JK
authors: Suh
authors: Sungwoo
authors: S
authors: Hong
authors: Soon-Sun
authors: SS
authors: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D013449:Sulfonamides; C577242:ethyl 6-(5-(phenylsulfonamido)pyridin-3-yl)imidazo(1,2-a)pyridine-3-carboxylate; D051057:Proto-Oncogene Proteins c-akt