title: Relaxin Inhibits High Glucose-Induced Matrix Accumulation in Human Mesangial Cells by Interfering with TGF-β1 Production and Mesangial Cells Phenotypic Transition.
abstract: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). DN is characterized by glomerular extracellular matrix accumulation, mesangial expansion, basement membrane thickening, and renal interstitial fibrosis. To date, mounting evidence has shown that H2 relaxin possesses powerful antifibrosis properties; however, the mechanisms of H2 relaxin on diabetic nephropathy remain unknown. Here, we aimed to explore whether H2 relaxin can reduce production of extracellular matrix (ECM) secreted by human mesangial cells (HMC). HMC were exposed to 5.5 mM glucose (NG) or 30 mM glucose (HG) with or without H2 relaxin. Fibronectin (FN) and collagen type IV levels in the culture supernatants were examined by solid-phase enzyme-linked immunoadsorbent assay (ELISA). Western blot was used to detect the expression of α-smooth muscle actin (α-SMA) protein. Quantitative polymerase chain reaction (qPCR) method was employed to analyze transforming growth factor (TGF)-β1 mRNA expression. Compared with the normal glucose group, the levels of fibronectin and collagen type were markedly increased after being cultured in high glucose medium. Compared with the high glucose group, remarkable decreases of fibronectin, collagen type IV, α-smooth muscle actin, and TGF-β1 mRNA expression were observed in the H2 relaxin-treated group. The mechanism by which H2 relaxin reduced high glucose-induced overproduction of ECM may be associated with inhibition of TGF-β1 mRNA expression and mesangial cells' phenotypic transition. H2 relaxin is a potentially effective modality for the treatment of DN.
authors.affiliation: Department of Nephrology, Hangzhou First People's Hospital, Affiliated Hangzhou Hospital of Nanjing Medical University.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Xie
authors.forename: Wenkai
authors.initials: W
authors.lastname: Xia
authors.forename: Xiao
authors.initials: X
authors.lastname: Fei
authors.forename: Qunhong
authors.initials: Q
authors.lastname: Xu
authors.forename: Xiu
authors.initials: X
authors.lastname: Yang
authors.forename: Donghao
authors.initials: D
authors.lastname: Qiu
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D012065:Relaxin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024141:Collagen Type IV; D005353:Fibronectins; C095068:RLN2 protein, human; D053773:Transforming Growth Factor beta1; D012065:Relaxin; D005947:Glucose