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Antifibrotic effect of tamoxifen in a model of progressive renal disease.
Dellê, Humberto; Rocha, José Roberto C; Cavaglieri, Rita C; Vieira, José Mauro; Malheiros, Denise M A C; Noronha, Irene L.
Afiliação
  • Dellê H; Laboratory of Cellular, Genetic, and Molecular Nephrology, University of São Paulo, Av. Dr. Arnaldo, 455, 4th Floor, Lab 4304, São Paulo, CEP 01246-903, Brazil.
J Am Soc Nephrol ; 23(1): 37-48, 2012 Jan.
Article em En | MEDLINE | ID: mdl-22052053
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-ß1 and plasminogen activator inhibitor-1, and with a significant reduction in α-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1ß- 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-ß1 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-ß1, suggesting that it may have therapeutic use in CKD treatment.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tamoxifeno / Antineoplásicos Hormonais / Fibroblastos / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Tamoxifeno / Antineoplásicos Hormonais / Fibroblastos / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: J Am Soc Nephrol Assunto da revista: NEFROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil