title: Anti-fibrotic effect of wogonin in renal tubular epithelial cells via Smad3-dependent mechanisms.
abstract: Renal fibrosis, a common feature and leading cause for End Stage Renal Disease, still lacks effective therapy. In the current study, we detected and compared the anti-fibrotic effects of wogonin and wogonoside, two major components of Scutellaria baicalensis Georgi, in TGF-β1-treated tubular epithelial cells of human and murine origins. Results consistently showed that compared with wogonoside, wogonin inhibits TGF-β1-induced upregulated mRNA and protein levels of collagen I and α-SMA with more efficiency, which was further confirmed by the immunofluorescence results that wogonin decreased the percentage of collagen I and α-SMA positive cells in TGF-β1-treated tubular epithelial cells. Mechanistically, wogonin mainly decreased Smad3 phosphorylation, but had marginal effect on non-canonical TGF-β signaling pathways, such as p38 and ERK MAP Kinase. Furthermore, in the cells deficient for TGF-β signaling or downstream Smad3, results demonstrated that even high concentration of wogonin failed to further decrease the level of collagen I and α-SMA, indicating the essential role of TGF-β/Smad3 signaling inhibition in the therapeutic action of wogonin in TGF-β1-stimulated tubular epithelial cells. Collectively, our results indicated that wogonin may be utilized as a potential anti-fibrotic Traditional Chinese Medicine monomer in the treatment of renal fibrosis.
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China; Institute for Kidney Diseases of Anhui Medical University, Anhui, China.
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Gui-Ling
authors.initials: GL
authors.lastname: Ren
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Hai-Di
authors.initials: HD
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China.
authors.forename: Zeng
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China.
authors.forename: Xiong-Wen
authors.initials: XW
authors.lastname: Lv
authors.affiliation: School of Pharmacy, Anhui Medical University, Anhui, China; Anhui Institute of Innovative Drugs, Anhui, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency / Q000378:metabolism; D051900:Smad3 Protein / Q000172:deficiency / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D044950:Flavanones; D005960:Glucosides; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C473995:wogonoside
keywords: Renal fibrosis; Smad3; TGF-β1; Wogonin