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Article: Petchiether A attenuates obstructive nephropathy by suppressing TGF-β/Smad3 and NF-κB signalling

TitlePetchiether A attenuates obstructive nephropathy by suppressing TGF-β/Smad3 and NF-κB signalling
Authors
KeywordsFibrosis
NF-κB
Obstructive nephropathy
Petchiether A
TGF-β/Smad3
Issue Date2019
PublisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838
Citation
Journal of Cellular and Molecular Medicine, 2019, v. 23 n. 8, p. 5576-5587 How to Cite?
AbstractObstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor-β1 (TGF-β1)/Smad3-driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small-molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF-β1-induced 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-1β and tumour necrosis factor-α) and reducing extracellular matrix deposition (α-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down-regulated the expression of the fibrotic marker collagen I in TGF-β1-treated renal epithelial cells. Further, we found that petA dose-dependently suppressed Smad3-responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF-β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF-β/Smad3 signalling.
Persistent Identifierhttp://hdl.handle.net/10722/272518
ISSN
2012 Impact Factor: 4.753
2015 SCImago Journal Rankings: 1.941
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYou, Y-
dc.contributor.authorLuo, Q-
dc.contributor.authorWu, W-
dc.contributor.authorZhang, J-
dc.contributor.authorZhu, H-
dc.contributor.authorLao, L-
dc.contributor.authorLan, HY-
dc.contributor.authorChen, H-
dc.contributor.authorCheng, Y-
dc.date.accessioned2019-07-20T10:43:49Z-
dc.date.available2019-07-20T10:43:49Z-
dc.date.issued2019-
dc.identifier.citationJournal of Cellular and Molecular Medicine, 2019, v. 23 n. 8, p. 5576-5587-
dc.identifier.issn1582-1838-
dc.identifier.urihttp://hdl.handle.net/10722/272518-
dc.description.abstractObstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor-β1 (TGF-β1)/Smad3-driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small-molecule meroterpenoid from Ganoderma, as a potential inhibitor of TGF-β1-induced 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-1β and tumour necrosis factor-α) and reducing extracellular matrix deposition (α-smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF-κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down-regulated the expression of the fibrotic marker collagen I in TGF-β1-treated renal epithelial cells. Further, we found that petA dose-dependently suppressed Smad3-responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF-β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF-β/Smad3 signalling.-
dc.languageeng-
dc.publisherWiley Open Access for Foundation for Cellular and Molecular Medicine. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1582-1838-
dc.relation.ispartofJournal of Cellular and Molecular Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectFibrosis-
dc.subjectNF-κB-
dc.subjectObstructive nephropathy-
dc.subjectPetchiether A-
dc.subjectTGF-β/Smad3-
dc.titlePetchiether A attenuates obstructive nephropathy by suppressing TGF-β/Smad3 and NF-κB signalling-
dc.typeArticle-
dc.identifier.emailYou, Y: yongke@hku.hk-
dc.identifier.emailLao, L: lxlao1@hku.hk-
dc.identifier.emailChen, H: haiyong@hku.hk-
dc.identifier.authorityLao, L=rp01784-
dc.identifier.authorityChen, H=rp01923-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1111/jcmm.14454-
dc.identifier.pmid31211499-
dc.identifier.pmcidPMC6652659-
dc.identifier.scopuseid_2-s2.0-85067479266-
dc.identifier.hkuros298741-
dc.identifier.volume23-
dc.identifier.issue8-
dc.identifier.spage5576-
dc.identifier.epage5587-
dc.publisher.placeUnited Kingdom-

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