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Transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21)\/Smad3\u2010driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small\u2010molecule meroterpenoid from <jats:italic>Ganoderma<\/jats:italic>, as a potential inhibitor of TGF\u2010\u03b21\u2010induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA\/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin\u20101\u03b2 and tumour necrosis factor\u2010\u03b1) and reducing extracellular matrix deposition (\u03b1\u2010smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF\u2010\u03baB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down\u2010regulated the expression of the fibrotic marker collagen I in TGF\u2010\u03b21\u2010treated renal epithelial cells. Further, we found that petA dose\u2010dependently suppressed Smad3\u2010responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF\u2010\u03b2\/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF\u2010\u03b2\/Smad3 signalling.<\/jats:p>","DOI":"10.1111\/jcmm.14454","type":"journal-article","created":{"date-parts":[[2019,6,18]],"date-time":"2019-06-18T12:34:03Z","timestamp":1560861243000},"page":"5576-5587","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Petchiether A attenuates obstructive nephropathy by suppressing TGF\u2010\u03b2\/Smad3 and NF\u2010\u03baB signalling"],"prefix":"10.1111","volume":"23","author":[{"given":"Yong\u2010Ke","family":"You","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China"},{"name":"Department of Chinese Medicine The University of Hong Kong\u2010Shenzhen Hospital Shenzhen 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