High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct

Abstract Growing evidence indicates that prorenin receptor (PRR) is upregulated in collecting duct (CD) of diabetic kidney. Prorenin is secreted by the principal CD cells, and is the natural ligand of the PRR. PRR activation stimulates fibrotic factors, including fibronectin, collagen, and transform...

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Autores principales:	Venkateswara R. Gogulamudi, Danielle Y. Arita, Camille R. T. Bourgeois, Justine Jorgensen, Jing He, William C. Wimley, Ryosuke Satou, Alexis A. Gonzalez, Minolfa C. Prieto
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a8a795260c5844b2a75c6453cf8deb72
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spelling	oai:doaj.org-article:a8a795260c5844b2a75c6453cf8deb722021-12-02T16:14:47ZHigh glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct10.1038/s41598-021-93296-42045-2322https://doaj.org/article/a8a795260c5844b2a75c6453cf8deb722021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93296-4https://doaj.org/toc/2045-2322Abstract Growing evidence indicates that prorenin receptor (PRR) is upregulated in collecting duct (CD) of diabetic kidney. Prorenin is secreted by the principal CD cells, and is the natural ligand of the PRR. PRR activation stimulates fibrotic factors, including fibronectin, collagen, and transforming growth factor-β (TGF-β) contributing to tubular fibrosis. However, whether high glucose (HG) contributes to this effect is unknown. We tested the hypothesis that HG increases the abundance of PRR at the plasma membrane of the CD cells, thus contributing to the stimulation of downstream fibrotic factors, including TGF-β, collagen I, and fibronectin. We used streptozotocin (STZ) male Sprague–Dawley rats to induce hyperglycemia for 7 days. At the end of the study, STZ-induced rats showed increased prorenin, renin, and angiotensin (Ang) II in the renal inner medulla and urine, along with augmented downstream fibrotic factors TGF-β, collagen I, and fibronectin. STZ rats showed upregulation of PRR in the renal medulla and preferential distribution of PRR on the apical aspect of the CD cells. Cultured CD M-1 cells treated with HG (25 mM for 1 h) showed increased PRR in plasma membrane fractions compared to cells treated with normal glucose (5 mM). Increased apical PRR was accompanied by upregulation of TGF-β, collagen I, and fibronectin, while PRR knockdown prevented these effects. Fluorescence resonance energy transfer experiments in M-1 cells demonstrated augmented prorenin activity during HG conditions. The data indicate HG stimulates profibrotic factors by inducing PRR translocation to the plasma membrane in CD cells, which in perspective, might be a novel mechanism underlying the development of tubulointerstitial fibrosis in diabetes mellitus.Venkateswara R. GogulamudiDanielle Y. AritaCamille R. T. BourgeoisJustine JorgensenJing HeWilliam C. WimleyRyosuke SatouAlexis A. GonzalezMinolfa C. PrietoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Venkateswara R. Gogulamudi Danielle Y. Arita Camille R. T. Bourgeois Justine Jorgensen Jing He William C. Wimley Ryosuke Satou Alexis A. Gonzalez Minolfa C. Prieto High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
description	Abstract Growing evidence indicates that prorenin receptor (PRR) is upregulated in collecting duct (CD) of diabetic kidney. Prorenin is secreted by the principal CD cells, and is the natural ligand of the PRR. PRR activation stimulates fibrotic factors, including fibronectin, collagen, and transforming growth factor-β (TGF-β) contributing to tubular fibrosis. However, whether high glucose (HG) contributes to this effect is unknown. We tested the hypothesis that HG increases the abundance of PRR at the plasma membrane of the CD cells, thus contributing to the stimulation of downstream fibrotic factors, including TGF-β, collagen I, and fibronectin. We used streptozotocin (STZ) male Sprague–Dawley rats to induce hyperglycemia for 7 days. At the end of the study, STZ-induced rats showed increased prorenin, renin, and angiotensin (Ang) II in the renal inner medulla and urine, along with augmented downstream fibrotic factors TGF-β, collagen I, and fibronectin. STZ rats showed upregulation of PRR in the renal medulla and preferential distribution of PRR on the apical aspect of the CD cells. Cultured CD M-1 cells treated with HG (25 mM for 1 h) showed increased PRR in plasma membrane fractions compared to cells treated with normal glucose (5 mM). Increased apical PRR was accompanied by upregulation of TGF-β, collagen I, and fibronectin, while PRR knockdown prevented these effects. Fluorescence resonance energy transfer experiments in M-1 cells demonstrated augmented prorenin activity during HG conditions. The data indicate HG stimulates profibrotic factors by inducing PRR translocation to the plasma membrane in CD cells, which in perspective, might be a novel mechanism underlying the development of tubulointerstitial fibrosis in diabetes mellitus.
format	article
author	Venkateswara R. Gogulamudi Danielle Y. Arita Camille R. T. Bourgeois Justine Jorgensen Jing He William C. Wimley Ryosuke Satou Alexis A. Gonzalez Minolfa C. Prieto
author_facet	Venkateswara R. Gogulamudi Danielle Y. Arita Camille R. T. Bourgeois Justine Jorgensen Jing He William C. Wimley Ryosuke Satou Alexis A. Gonzalez Minolfa C. Prieto
author_sort	Venkateswara R. Gogulamudi
title	High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
title_short	High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
title_full	High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
title_fullStr	High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
title_full_unstemmed	High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
title_sort	high glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a8a795260c5844b2a75c6453cf8deb72
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High glucose induces trafficking of prorenin receptor and stimulates profibrotic factors in the collecting duct

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