Soluble uric acid increases intracellular calcium through an angiotensin II-dependent mechanism in immortalized human mesangial cells.
Hyperuricemia is associated with increases in cardiovascular risk and renal disease. Mesangial cells regulate glomerular filtration rates through the release of hormones and vasoactive substances. This study evaluates the signaling pathway of uric acid (UA) in immortalized human mesangial cells (ihMCs). To evaluate cell proliferation, ihMCs were exposed to UA (6-10 mg/dL) for 24-144 h. In further experiments, ihMCs were treated with UA (6-10 mg/dL) for 12 and 24 h simultaneously with losartan (10(-7) mmol/L). Angiotensin II (AII) and endothelin-1 (ET-1) were assessed using the enzyme-linked immunosorbent assay (ELISA) technique. Pre-pro-ET mRNA was evaluated by the real-time PCR technique. It was observed that soluble UA (8 and 10 mg/dL) stimulated cellular proliferation. UA (10 mg/dL) for 12 h significantly increased AII protein synthesis and ET-1 expression and protein production was increased after 24 h. Furthermore, UA increased [Ca(2+)](i), and this effect was significantly blocked when ihMCs were preincubated with losartan. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. In addition, UA can potentially affect glomerular function due to UA-induced proliferation and contraction of mesangial cells. The latter mechanism could be related to the long-term effects of UA on renal function and chronic kidney disease.
Albertoni
Guilherme
G
Department of Medicine, Nephrology Division, Federal University of São Paulo, Rua Pedro de Toledo 740, São Paulo, Brazil. albertonig@nefro.epm.br
Maquigussa
Edgar
E
Pessoa
Edson
E
Barreto
Jose Augusto
JA
Borges
Fernanda
F
Schor
Nestor
N
D000804:Angiotensin II / Q000096:biosynthesis / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D002118:Calcium / Q000032:analysis*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D050527:Mesangial Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D016133:Polymerase Chain Reaction; D014527:Uric Acid / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D019332:Endothelin-1; D000804:Angiotensin II; D014527:Uric Acid; D019808:Losartan; D002118:Calcium