Antifibrotic Effect of Tamoxifen in a Model of Progressive Renal Disease

Autor(es)

Delle, Humberto ^[1] ; Rocha, Jose Roberto C. ^[2] ; Cavaglieri, Rita C. ^[1] ; Vieira, Jr., Jose Mauro ^[1] ; Malheiros, Denise M. A. C. ^[1] ; Noronha, Irene L. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Cellular Genet & Mol Nephrol, BR-01246903 Sao Paulo - Brazil

^[2] Carlos Chagas Inst, Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY; v. 23, n. 1, p. 37-48, JAN 2012.
• Citações Web of Science: 34

Resumo

Tamoxifen, a selective estrogen receptor modulator, has antifibrotic properties; however, whether it can attenuate renal fibrosis is unknown. In this study, we tested the effects of tamoxifen in a model of hypertensive nephrosclerosis (chronic inhibition of nitric oxide synthesis with L-NAME). After 30 days, treated rats had significantly lower levels of albuminuria as well as lower histologic scores for glomerulosclerosis and interstitial fibrosis than untreated controls. Tamoxifen was renoprotective despite having no effect on the sustained, severe hypertension induced by L-NAME. Tamoxifen prevented the accumulation of extracellular matrix by decreasing the expression of collagen I, collagen III, and fibronectin mRNA and protein. These renoprotective effects associated with inhibition of TGF-beta 1 and plasminogen activator inhibitor-1, and with a significant reduction in a-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1 beta- and angiotensin-II-induced proliferation of fibroblasts from both kidney explants and from the NRK-49F cell line. Tamoxifen also inhibited the expression of extracellular matrix components and the production and release of TGF-beta 1 into the supernatant of these cells. In summary, tamoxifen exhibits antifibrotic effects in the L-NAME model of hypertensive nephrosclerosis, likely through the inhibition of TGF-beta 1, suggesting that it may have therapeutic use in CKD treatment. (AU)

• Processo FAPESP: 01/01452-5 - Estudo do sistema renina-angiotensina intra-renal em modelo experimental de nefropatia cronica progressiva.
• Beneficiário: Irene de Lourdes Noronha
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/05837-9 - Efeito do anti-estrogenico tamoxifeno na fibrose intersticial renal em dois modelos experimentais: inibicao cronica da sintese do oxido nitrico e obstrucao ureteral unilateral.
• Beneficiário: Humberto Dellê
• Modalidade de apoio: Bolsas no Brasil - Mestrado