Activation of annexin A1 signalling in renal fibroblasts exerts antifibrotic effects

Acta Physiologica
H NeymeyerA Paliege

Abstract

The anti-inflammatory protein annexin A1 (AnxA1) and its formyl peptide receptor 2 (FPR2) have protective effects in organ fibrosis. Their role in chronic kidney disease (CKD) has not yet been elucidated. Our aim was to characterize the AnxA1/FPR2 system in models of renal fibrosis. Rats were treated with angiotensin receptor antagonist during the nephrogenic period (ARAnp) to induce late-onset hypertensive nephropathy and fibrosis. Localization and regulation of AnxA1 and FPR2 were studied by quantitative real-time PCR and double labelling immunofluorescence. Biological effects of AnxA1 were studied in cultured renal fibroblasts from AnxA1(-/-) and wild-type mice. Angiotensin receptor antagonist during the nephrogenic period kidneys displayed matrix foci containing CD73(+) fibroblasts, alpha-smooth muscle actin (a-SMA)(+) myofibroblasts and CD68(+) macrophages. TGF-β and AnxA1 mRNAs were ~threefold higher than in controls. AnxA1 was localized to macrophages and fibroblasts; myofibroblasts were negative. FPR2 was localized to fibroblasts, myofibroblasts, macrophages and endothelial cells. AnxA1 and FPR2 immunoreactive signals were increased in the foci, with fibroblasts and macrophages expressing both proteins. AnxA1(-/-) fibro...Continue Reading

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Citations

Apr 17, 2016·Acta Physiologica·P B Persson
Mar 31, 2016·Acta Physiologica·P B Persson
Mar 28, 2017·Acta Physiologica·A Zakrisson, C Kronfoth
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Jul 21, 2021·Nature Reviews. Nephrology·Eoin BrennanCatherine Godson
Sep 17, 2021·Proceedings of the National Academy of Sciences of the United States of America·Jianmin ChenDianne Cooper

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