Mesangial cells regulate the single nephron GFR and preserve the integrity of the glomerular filtration barrier: An intravital multiphoton microscopy study

Ziegler, Vera and Fremter, Katharina and Helmchen, Julia and Witzgall, Ralph and Castrop, Hayo (2021) Mesangial cells regulate the single nephron GFR and preserve the integrity of the glomerular filtration barrier: An intravital multiphoton microscopy study. ACTA PHYSIOLOGICA, 231 (4): e13592. ISSN 1748-1708, 1748-1716

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Abstract

Aim The intraglomerular mesangial cells are located between the glomerular capillaries. Here we hypothesized that mesangial cells regulate the single nephron glomerular filtration rate (snGFR) and that mesangial cells support the integrity of the glomerular filtration barrier. Methods We assessed the function of mesangial cells in vivo by multiphoton microscopy. Mesangial cells were depleted in Munich Wistar Froemter rats using the Thy1.1 antibody model. Results The Thy1.1 antibody caused the cell-specific loss of 82 +/- 3% of mesangial cells. After mesangial cell depletion, the baseline snGFR was reduced to 12.0 +/- 1.2 vs 32.4 +/- 3.2 nL/min in controls. In control rats, the snGFR decreased after angiotensin II infusion by 61 +/- 3% (P = .004), whereas it remained unchanged in Thy1.1-treated rats. The changes in the snGFR after angiotensin II infusion in control rats were accompanied by the marked rotation of the capillary loops within Bowman's space. This phenomenon was absent in anti-Thy1.1-treated rats. The glomerular sieving coefficient (GSC(A)) for albumin, used as a measure of the integrity of the glomerular filtration barrier, was low in control rats (0.00061 +/- 0.00004) and increased after angiotensin II infusion (0.00121 +/- 0.00015). In Thy1.1-treated rats, the GSC was elevated (0.0032 +/- 0.00059) and did not change in response to angiotensin II. Electron microscopy revealed the increased thickness of the glomerular basement membrane after mesangial cell depletion. Conclusion Our data suggest that mesangial cells actively contribute to the regulation of the snGFR. Furthermore, mesangial cells are crucially involved in maintaining the integrity of the glomerular filtration barrier, in part by modulating the thickness of the glomerular basement membrane.

Item Type: Article
Uncontrolled Keywords: ; glomerular basement membrane; glomerular sieving coefficient of albumin; intravital microscopy; mesangial cells; regulation of glomerular filtration rate
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Wolf Hayo Castrop
Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall
Depositing User: Dr. Gernot Deinzer
Date Deposited: 13 Jul 2022 09:03
Last Modified: 13 Jul 2022 09:03
URI: https://pred.uni-regensburg.de/id/eprint/45741

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