Unique Regulatory Properties of Mesangial Cells Are Genetically Determined in the Rat

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Oct 25

PMID 25343449

Citations 3

Authors

Ping-Chin Lai

Ling-Yin Chiu

Prashant Srivastava

Cristina Trento

Francesco Dazzi

Enrico Petretto

H Terence Cook

Jacques Behmoaras

Affiliations

Soon will be listed here.

Abstract

Mesangial cells are glomerular cells of stromal origin. During immune complex mediated crescentic glomerulonephritis (Crgn), infiltrating and proliferating pro-inflammatory macrophages lead to crescent formation. Here we have hypothesised that mesangial cells, given their mesenchymal stromal origin, show similar immunomodulatory properties as mesenchymal stem cells (MSCs), by regulating macrophage function associated with glomerular crescent formation. We show that rat mesangial cells suppress conA-stimulated splenocyte proliferation in vitro, as previously shown for MSCs. We then investigated mesangial cell-macrophage interaction by using mesangial cells isolated from nephrotoxic nephritis (NTN)-susceptible Wistar Kyoto (WKY) and NTN-resistant Lewis (LEW) rats. We first determined the mesangial cell transcriptome in WKY and LEW rats and showed that this is under marked genetic control. Supernatant transfer results show that WKY mesangial cells shift bone marrow derived macrophage (BMDM) phenotype to M1 or M2 according to the genetic background (WKY or LEW) of the BMDMs. Interestingly, these effects were different when compared to those of MSCs suggesting that mesangial cells can have unique immunomodulatory effects in the kidney. These results demonstrate the importance of the genetic background in the immunosuppressive effects of cells of stromal origin and specifically of mesangial cell-macrophage interactions in the pathophysiology of crescentic glomerulonephritis.

Citing Articles

Immunomodulatory Properties of Mesenchymal Stromal Cells Can Vary in Genetically Modified Rats.

Vallant N, Sandhu B, Hamaoui K, Prendecki M, Pusey C, Papalois V Int J Mol Sci. 2021; 22(3).

PMID: 33504032 PMC: 7865849. DOI: 10.3390/ijms22031181.

Identification of Ceruloplasmin as a Gene that Affects Susceptibility to Glomerulonephritis Through Macrophage Function.

Chen T, Rotival M, Chiu L, Bagnati M, Ko J, Srivastava P Genetics. 2017; 206(2):1139-1151.

PMID: 28450461 PMC: 5499168. DOI: 10.1534/genetics.116.197376.

Endothelin and the glomerulus in chronic kidney disease.

Barton M, Sorokin A Semin Nephrol. 2015; 35(2):156-67.

PMID: 25966347 PMC: 4731878. DOI: 10.1016/j.semnephrol.2015.02.005.

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