title: Plasma Gelsolin Induced Glomerular Fibrosis via the TGF-β1/Smads Signal Transduction Pathway in IgA Nephropathy.
abstract: Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway. This is supported by the following findings: human mesangial cells (HMCs) show remarkable morphological changes and proliferation in response to co-stimulation with pGSN and polymeric IgA1 (pIgA1) from IgAN patients compared to other controls. Moreover, ELISA assays showed that more TGF-β1 secretion was found in HMCs supernatants in the co-stimulation group. Further experiments showed increased TGF-β1, Smad3, p-Smad2/3, Smad4, and collagen 1 and decreased Smad7 expression in the co-stimulation group. Our present study implied that the synergistic effect of pGSN and pIgA induced glomerular fibrosis via the TGF-β1/Smads signal transduction pathway. This might be a potential mechanism for the glomerular fibrosis observed in IgAN patients.
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. Zhangleiyy12@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. han050122@163.com.
authors.forename: Changsong
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. yefeiboer@163.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. he_yan419@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. jinyinji66@126.com.
authors.forename: Yinji
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. wtzpath@163.com.
authors.forename: Tianzhen
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. wuyiqidd@126.com.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. jiangyang1978@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Microbiology, Harbin Medical University, Harbin 150081, China. fengminzhang@ems.hrbmu.edu.cn.
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Harbin Medical University, Harbin 150081, China. jinxm5554@163.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Jin
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D049109:Cell Proliferation; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D018260:Gelsolin / Q000097:blood*; D005922:Glomerulonephritis, IGA / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018260:Gelsolin; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1
keywords: IgA nephropathy; TGF-β1/Smadssignal transduction pathway; glomerular fibrosis; plasma gelsolin