title: In silico prediction of specific pathways that regulate mesangial cell proliferation in IgA nephropathy.
abstract: IgA nephropathy is one of the most common forms of primary glomerulonephritis worldwide leading to end-stage renal disease. Proliferation of mesangial cells, i.e., the multifunctional cells located in the intracapillary region of glomeruli, after IgA- dominant immune deposition is the major histologic feature in IgA nephropathy. In spite of several studies on molecular basis of proliferation in these cells, specific pathways responsible for regulation of proliferation are still to be discovered. In this study, we predicted a specific signaling pathway started from transferrin receptor (TFRC), a specific IgA1 receptor on mesangial cells, toward a set of proliferation-related proteins. The final constructed subnetwork was presented after filtration and evaluation. The results suggest that estrogen receptor (ESR1) as a hub protein in the significant subnetwork has an important role in the mesangial cell proliferation and is a potential target for IgA nephropathy therapy. In conclusion, this study suggests a novel hypothesis for the mechanism of pathogenesis in IgA nephropathy and is a reasonable start point for the future experimental studies on mesangial proliferation process in this disease.
authors.affiliation: School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Elham Sadat
authors.initials: ES
authors.lastname: Mirfazeli
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Sayed-Amir
authors.initials: SA
authors.lastname: Marashi
authors.affiliation: Chronic Kidney Disease Research Center (CKDRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: shiva.kalantari@sbmu.ac.ir.
authors.forename: Shiva
authors.initials: S
authors.lastname: Kalantari
mesh_terms: D000818:Animals; D001706:Biopsy; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005374:Filtration; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D050527:Mesangial Cells / Q000166:cytology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D007070:Immunoglobulin A; D011960:Receptors, Estrogen; D011990:Receptors, Transferrin
keywords: Estrogen receptor; IgA nephropathy; Mesangial proliferation; Systems biology; Transferrin receptor