title: Acid loading stimulates rat glomerular mesangial cells proliferation through Na(+)-H (+) exchanger isoform 1 (NHE1)-dependent pathway.
abstract: The role of metabolic acidosis in the progression of chronic kidney disease (CKD) remains unclear. The aim of the present study was to investigate the direct effects of acid loading on the proliferation of rat glomerular mesangial cells (GMCs) in vitro and the possible role of sodium-hydrogen ion exchanger isoform 1 (NHE1). Rat GMCs were treated with acidic medium as acid loading. Growth and proliferation of GMCs was studied by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, thymidine ((3)H-TdR) incorporation, and flow cytometry. NHE1 protein expression and activity were quantified by Western blot and dual wavelength epifluorescent illumination with 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein, respectively. 5-(N,N-dimethyl) amiloride hydrochloride (DMA), a specific inhibitor of NHE1, was used to investigate the possible involvement of NHE1 in the proliferation of GMCs. The MTT assay, (3)H-TdR incorporation, and cell cycle distribution analysis indicated that acid loading stimulated the proliferation of GMCs. Acid loading increased NHE1 activity, but had no effects on NHE1 expression at the protein level. The effects of acid loading on the proliferation of GMCs were inhibited by DMA. Acid loading induced GMC proliferation through NHE1-dependent pathways. Our findings may contribute to the understanding of metabolic acidosis in the progression of CKD.
authors.affiliation: Department of Pathophysiology, Institute of Digestive Disease, Tongji University School of Medicine, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Su
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Chang-Jie
authors.initials: CJ
authors.lastname: Chen
authors.forename: Yong-Yu
authors.initials: YY
authors.lastname: Li
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Lai
authors.forename: Ming-Min
authors.initials: MM
authors.lastname: Zhang
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Liu
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.forename: Ai
authors.initials: A
authors.lastname: Peng
authors.forename: Chuan-Ming
authors.initials: CM
authors.lastname: Hao
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Shan-Yan
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D018450:Disease Progression; D005434:Flow Cytometry; D005452:Fluoresceins / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D050527:Mesangial Cells / Q000378:metabolism*; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013194:Staining and Labeling; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D005452:Fluoresceins; C452850:Slc9a1 protein, rat; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013778:Tetrazolium Salts; D013844:Thiazoles; C039465:5-dimethylamiloride; D000584:Amiloride; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; C022616:thiazolyl blue
references.citation: J Mol Cell Cardiol. 2008 Apr;44(4):647-53
references.pmid: 18329039
references.citation: Channels (Austin). 2008 Sep-Oct;2(5):329-36
references.pmid: 19001864
references.citation: J Biol Chem. 1993 Feb 15;268(5):3396-400
references.pmid: 8381429
references.citation: Basic Res Cardiol. 2011 Jun;106(4):603-16
references.pmid: 21359875
references.citation: Nephrol Dial Transplant. 2012 Aug;27(8):3056-62
references.pmid: 22851628
references.citation: J Clin Invest. 1985 Aug;76(2):667-75
references.pmid: 2993363
references.citation: J Surg Res. 2013 May;181(2):e75-81
references.pmid: 22878146
references.citation: Curr Opin Cell Biol. 2000 Feb;12(1):104-12
references.pmid: 10679366
references.citation: J Cell Biol. 2000 Jul 10;150(1):213-24
references.pmid: 10893269
references.citation: Kidney Int. 2010 Apr;77(7):617-23
references.pmid: 20072112
references.citation: Ren Fail. 2009;31(8):726-35
references.pmid: 19814640
references.citation: Kidney Int. 1998 Jun;53(6):1706-12
references.pmid: 9607203
references.citation: J Biol Chem. 2000 Mar 17;275(11):7942-9
references.pmid: 10713111
references.citation: Kidney Int. 2000 Jun;57(6):2258-67
references.pmid: 10844596
references.citation: J Biol Chem. 2004 Jan 16;279(3):1845-52
references.pmid: 14600156
references.citation: Cell Tissue Res. 2012 Jan;347(1):141-54
references.pmid: 22105921
references.citation: Lancet. 2010 Apr 10;375(9722):1296-309
references.pmid: 20382326
references.citation: Annu Rev Pharmacol Toxicol. 2002;42:527-52
references.pmid: 11807182
references.citation: Curr Opin Nephrol Hypertens. 2012 Sep;21(5):552-6
references.pmid: 22874469
references.citation: Am J Kidney Dis. 2011 May;57(5):781-7
references.pmid: 21349616
references.citation: Am J Nephrol. 2010;31(1):75-82
references.pmid: 19893300
references.citation: Kidney Int. 2010 Dec;78(11):1128-35
references.pmid: 20861823
references.citation: Nephrol Dial Transplant. 2012 Aug;27(8):3063-71
references.pmid: 22851629
references.citation: Kidney Int. 2004 Apr;65(4):1224-30
references.pmid: 15086461
references.citation: Kidney Int. 2008 Jun;73(11):1216-9
references.pmid: 18322541
references.citation: Am J Kidney Dis. 2003 Mar;41(3 Suppl 1):S3-7
references.pmid: 12612942
references.citation: Am J Physiol. 1965 Jun;208:1135-42
references.pmid: 14301369