NDLI: Berberine inhibits Smad and non-Smad signaling cascades and enhances autophagy against pulmonary fibrosis

Content Provider	Springer Nature Link
Author	Chitra, Palanivel Saiprasad, Gowrikumar Manikandan, Ramar Sudhandiran, Ganapasam
Copyright Year	2015
Abstract	Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disorder of unknown aetiology. Transforming growth factor-β1 (TGF-β1)-mediated Smad and non-Smad signaling cascades are considered as central players in accelerating pulmonary fibrosis. We earlier reported berberine’s amelioration against TGF-β1-mediated pro-fibrotic effects in bleomycin-induced pulmonary fibrosis. The present study aimed to determine the regulatory role of berberine on abrogated Smad 2/3 and FAK-dependent PI3K/Akt-mTOR signaling cascades in bleomycin-induced pulmonary fibrosis. Male Wistar rats were subjected to single intratracheal instillation of bleomycin (2.5 U/kg) on day 0, and berberine treatments were provided in either preventive or therapeutic modes, respectively. Berberine mitigated the elevated expression of fibrotic markers, α-smooth muscle actin (α-SMA), fibronectin, collagens I and III and reversed bleomycin-induced ultrastructural alterations in the lungs. Berberine inhibited the bleomycin-induced raise in p-Smad 2/3 and enhanced Smad 7 expression. Berberine blocked the activation of FAK and PI3K/Akt against bleomycin-induced dysregulation, with subsequent raise in PTEN expression. In addition, by inhibiting p-mTOR, berberine stimulated autophagy as evidenced by increase in Beclin-1, LC3-II levels with enhanced autophagosome formation. Cumulatively, through targeted inhibition of dysregulated Smad and FAK-dependent PI3K/Akt-mTOR signaling axis, berberine attenuated the fibrotic insults of bleomycin. Berberine inhibits Smad 2/3 activation and enhances Smad 7 in bleomycin-induced rat lungs. Bleomycin-induced activation of FAK is inhibited by berberine. Berberine inhibits bleomycin-induced activation of PI3K/Akt cascade. Berberine inhibits mTOR activation to enhance autophagy and suppresses fibrotic markers.
Starting Page	1015
Ending Page	1031
Page Count	17
File Format	PDF
ISSN	09462716
Journal	Journal of Molecular Medicine
Volume Number	93
Issue Number	9
e-ISSN	14321440
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2015-04-17
Publisher Place	Berlin/Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pulmonary fibrosis Smad FAK PI3K mTOR Autophagy Molecular Medicine Human Genetics Internal Medicine
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Genetics (clinical)

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