Lamin A/C in renal tubular cells is important for tissue repair, cell proliferation, and calcium oxalate crystal adhesion, and is associated with potential crystal receptors

Abstract

© FASEB. A previous study reported that lamin A/C (LMNA) expression was increased in renal tubular cells adhered with calcium oxalate monohydrate (COM) crystals; however, its functional significance in kidney stone disease remained unknown. In the present study, increased levels of LMNAand its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining.LMNAwas then knocked down bysmall interferingRNA.Immunofluorescence staining confirmed the efficiency of small interfering RNA of LMNA (si-LMNA), which also reduced expression of its partner, SYNE1. Scratch assay and total cell count revealed defects in tissue repair and cell proliferation, respectively, whereas cell death quantitation showed no cytotoxicity in si-LMNAtransfected cells. Crystal-binding assay highlighted the role of LMNA in crystal adhesion, whereas protein network analysis revealed interactions betweenLMNAand potentialCOMcrystal receptors.Their associationswere confirmedby reduced levels of these proteins, including vimentin, tubulin, enolase, S100, and annexin A2, in si-LMNAtransfected cells. These data have demonstrated for the first time, to our knowledge, that LMNA in renal tubular cells is important for tissue repair, cell proliferation, and COM crystal adhesion and is associated with potential COM crystal receptors. Therefore, LMNA may serve as a potential target for prevention of kidney stone disease and its recurrence. Pongsakul, N., Vinaiphat, A., Chanchaem, P., Fong-ngern, K., Thongboonkerd, V. Lamin A/C in renal tubular cells is important for tissue repair, cell proliferation, and calcium oxalate crystal adhesion, and is associated with potential crystal receptors.