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Intracrine action of angiotensin II in mesangial cells: subcellular distribution of angiotensin II receptor subtypes AT1 and AT2

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Abstract

Biological effects of angiotensin II (AngII) such as regulation of AngII target genes may be triggered by interaction of AngII with intracellular AngII receptor types 1 and 2 (AT1 and AT2), defined as intracrine response. The aim of this study was to examine the presence of AT1 and AT2 receptors in nuclear membrane of human mesangial cells (HMCs) and evaluate the possible biological effects mediated by intracellular AT1 through an intracrine mechanism. Subcellular distribution of AT1 and AT2 was evaluated by immunofluorescence and by western blot in isolated nuclear extract. Endogenous intracellular synthesis of AngII was stimulated by high glucose (HG). Effects of HG were analyzed in the presence of candesartan, which prevents AngII internalization. Both receptors were found in nuclear membrane. Fluorescein isothiocyanate (FITC)-labeled AngII added to isolated nuclei produced a fluorescence that was reduced in the presence of losartan or PD-123319 and quenched in the presence of both inhibitors simultaneously. HG induced overexpression of fibronectin and increased cell proliferation in the presence of candesartan, indicating an intracrine action of AngII induced by HG. Results showed the presence of nuclear receptors in HMCs that can be activated by AngII through an intracrine response independent of cytoplasmic membrane AngII receptors.

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Acknowledgements

The authors are acknowledge the support to this work under Grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível superior (CAPES), and Fundação Oswaldo Ramos, and are grateful to Laboratório Multiusuário 6 – Infar/Unifesp for their help in the analyses on Confocal Microscopy.

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  1. Renal Division, Department of Medicine, Federal University of São Paulo, Rua Pedro de Toledo, 781, São Paulo, SP, 04023-900, Brazil

    Antônio da Silva Novaes, Rosemara Silva Ribeiro, Luciana Guilhermino Pereira, Fernanda Teixeira Borges & Mirian Aparecida Boim

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  1. Antônio da Silva Novaes
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  2. Rosemara Silva Ribeiro
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  3. Luciana Guilhermino Pereira
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Correspondence to Mirian Aparecida Boim.

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da Silva Novaes, A., Ribeiro, R.S., Pereira, L.G. et al. Intracrine action of angiotensin II in mesangial cells: subcellular distribution of angiotensin II receptor subtypes AT1 and AT2. Mol Cell Biochem 448, 265–274 (2018). https://doi.org/10.1007/s11010-018-3331-y

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  • DOI: https://doi.org/10.1007/s11010-018-3331-y

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