title: Quercetin Inhibits Fibroblast Activation and Kidney Fibrosis Involving the Suppression of Mammalian Target of Rapamycin and β-catenin Signaling.
abstract: Quercetin, a flavonoid found in a wide variety of plants and presented in human diet, displays promising potential in preventing kidney fibroblast activation. However, whether quercetin can ameliorate kidney fibrosis in mice with obstructive nephropathy and the underlying mechanisms remain to be further elucidated. In this study, we found that administration of quercetin could largely ameliorate kidney interstitial fibrosis and macrophage accumulation in the kidneys with obstructive nephropathy. MTORC1, mTORC2, β-catenin as well as Smad signaling were activated in the obstructive kidneys, whereas quercetin could markedly reduce their abundance except Smad3 phosphorylation. In cultured NRK-49F cells, quercetin could inhibit α-SMA and fibronectin (FN) expression induced by TGFβ1 treatment. MTORC1, mTORC2, β-catenin and Smad signaling pathways were stimulated by TGFβ1 at a time dependent manner. Similar to those findings in the obstructive kidneys, mTORC1, mTORC2 and β-catenin, but not Smad signaling pathways were remarkably blocked by quercetin treatment. Together, these results suggest that quercetin inhibits fibroblast activation and kidney fibrosis involving a combined inhibition of mTOR and β-catenin signaling transduction, which may act as a therapeutic candidate for patients with chronic kidney diseases.
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Jiafa
authors.initials: J
authors.lastname: Ren
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Li
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gui
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.
authors.forename: Weichun
authors.initials: W
authors.lastname: He
authors.affiliation: Center for Kidney Diseases, 2nd Affiliated Hospital, Nanjing Medical University, 262 North Zhongshan Road, Nanjing, Jiangsu, China.|State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Dai
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D000071416:Twist Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005353:Fibronectins; D046912:Multiprotein Complexes; D051785:Smad Proteins; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; D000071416:Twist Transcription Factors; D051176:beta Catenin; D011794:Quercetin; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D058570:TOR Serine-Threonine Kinases