title: 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: 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 LMNA and its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining. LMNA was then knocked down by small interfering RNA. 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-LMNA-transfected cells. Crystal-binding assay highlighted the role of LMNA in crystal adhesion, whereas protein network analysis revealed interactions between LMNA and potential COM crystal receptors. Their associations were confirmed by reduced levels of these proteins, including vimentin, tubulin, enolase, S100, and annexin A2, in si-LMNA-transfected 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.
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Nutkridta
authors.initials: N
authors.lastname: Pongsakul
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Arada
authors.initials: A
authors.lastname: Vinaiphat
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Prangwalai
authors.initials: P
authors.lastname: Chanchaem
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand.
authors.forename: Kedsarin
authors.initials: K
authors.lastname: Fong-Ngern
authors.affiliation: Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, and Center for Research in Complex Systems Science, Mahidol University, Bangkok, Thailand thongboonkerd@dr.com.
authors.forename: Visith
authors.initials: V
authors.lastname: Thongboonkerd
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D004285:Dogs; D007684:Kidney Tubules / Q000378:metabolism*; D034904:Lamin Type A / Q000378:metabolism*; D034882:Lamins / Q000378:metabolism*; D061985:Madin Darby Canine Kidney Cells / Q000166:cytology
chemical_list: D034904:Lamin Type A; D034882:Lamins; D002129:Calcium Oxalate
keywords: LMNA; kidney stone; nephrolithiasis; prevention; protein network