TMEM63C, a Potential Novel Target for Albuminuria Development, Is Regulated by MicroRNA-564 and Transforming Growth Factor beta in Human Renal Cells

Abstract

<b><i>Introduction:</i></b> Transmembrane protein (TMEM) 63C is a member of the TMEM gene family and was recently linked to glomerular filtration barrier function and albuminuria. Its molecular function and expression regulation are largely unknown. <b><i>Objective:</i></b> In this study, we set out to characterize the regulating impact of microRNAs (miRNAs) such as miRNA-564 (miR-564) on TMEM63C expression in renal cells. Also, we examined the influence of transforming growth factor beta (TGF-ß) on TMEM63C expression and the potential impact of TMEM63C inhibition on epithelial-mesenchymal transition (EMT) in renal cells and on cell viability in human embryonic kidney 293 cells (HEK 293). <b><i>Methods:</i></b> Expression analyses were done using real-time PCR and Western blot. Dual luciferase assay was performed to determine the miRNA-mediated expression control. Cell viability was assessed via trypan blue exclusion staining. <b><i>Results and Conclusions:</i></b> MiR-564 reduced TMEM63C expression in HEK 293 and human podocytes (hPC). The treatment of renal cells with TGF-ß led to an increased expression of TMEM63C. Moreover, a reduced TMEM63C expression was associated with a changed ratio of EMT marker proteins such as α-smooth muscle actin versus E-cadherin in HEK 293 and decreased nephrin expression in hPC. In addition, cell viability was reduced upon inhibition of TMEM63C expression in HEK 293. This study demonstrates first mechanisms involved in TMEM63C expression regulation and a link to EMT in renal cells.

Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis

“…Although the speci c functions of TMEM family proteins are still poorly characterized, new ndings have highlighted the importance of the TMEM family as prognostic markers for various diseases [33][34][35] . Among TMEM family proteins, TMEM45A has been reported to be correlated with epidermal keratinization through the Golgi network in both in vivo and in vitro models [36] .…”

Small Nucleolar RNAs in Pseudoexfoliation Glaucoma

“…Some studies have shown significantly reduced expression of TMEM136 in iris and ciliary body tissues in PEX patients [ 3 , 9 , 55 , 56 ]. TMEM63C ( locus 14q24.3 ) encodes transmembrane protein 63C, which enables calcium-activated cation channel activity and is involved in cation transport [ 57 , 58 ]. Calcium participates in regulating voltage-gated sodium, calcium, and potassium channels [ 59 ].…”

“…In a study on age-related macular degeneration, a suggestive association signal in TMEM63C was found, but its role in AMD pathogenesis is unknown [ 61 ]. Additionally, TMEM63C is considered a biomarker of focal segmental glomerulosclerosis (FSGS) [ 57 , 62 ]. FSGS shows the obliteration or collapse of glomerular capillary loops via increased ECM [ 63 ].…”