A novel PI3K inhibitor alleviates fibrotic responses in fibroblasts derived from Peyronie's plaques.

Abstract:

:Peyronie's disease (PD) is fibrosis localized in the tunica albuginea that is characterized by penile deformity and curvature. The pathogenesis of this disease remains unclear even though transforming growth factor-β (TGF-β)/smad signalling has been reported to be associated with PD. Recent studies have shown that phosphoinositide 3-kinase (PI3K)/Akt signalling regulates fibrotic responses including collagen synthesis and cell proliferation. Thus, we synthesized HS-173, a novel PI3K inhibitor, and determined whether this compound has anti-fibrotic effects on PD-derived primary fibroblasts. In this study, we found that HS-173 inhibited the growth of fibroblasts in a dose-dependent manner and induced apoptosis. In addition, HS-173 reduced the expression of α-smooth muscle actin (α-SMA), vimentin, PAI-1, fibronectin, collagen type I, collagen IV and TGF-β-activated smad2/3 in PD-derived primary fibroblasts. HS-173 blocked the PI3K/Akt signalling pathway by decreasing the activation of Akt, mTOR and P70S6K. Our results showed that HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signalling in PD-derived primary fibroblasts. Our findings provide molecular insights into the potential therapeutic action of HS-173 through targeting the PI3K/Akt pathway in PD-derived fibroblasts and demonstrated that HS-173 could be used as a pharmacological agent for treating other fibrotic diseases.

journal_name

Int J Oncol

authors

Jung KH,Ryu YL,Lee HS,Lee H,Son MK,Yan HH,Hong SW,Ryu JK,Hong S,Suh JK,Hong SS

doi

10.3892/ijo.2013.1905

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

2001-8

issue

6

eissn

1019-6439

issn

1791-2423

journal_volume

42

pub_type

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