Mast Cells and MCPT4 Chymase Promote Renal Impairment after Partial Ureteral Obstruction

Frontiers in Immunology
Maguelonne PonsUlrich Blank

Abstract

Obstructive nephropathy constitutes a major cause of pediatric renal progressive disease. The mechanisms leading to disease progression are still poorly understood. Kidney fibrotic lesions are reproduced using a model of partial unilateral ureteral obstruction (pUUO) in newborn mice. Based on data showing significant mast cell (MC) infiltration in patients, we investigated the role of MC and murine MCPT4, a MC-released chymase, in pUUO using MC- (W(sh/sh)), MCPT4-deficient (Mcpt4(-/-)), and wild-type (WT) mice. Measurement of kidney length and volume by magnetic resonance imaging (MRI) as well as postmortem kidney weight revealed hypotrophy of operated right kidneys (RKs) and compensatory hypertrophy of left kidneys. Differences between kidneys were major for WT, minimal for W(sh/sh), and intermediate for Mcpt4(-/-) mice. Fibrosis development was focal and increased only in WT-obstructed kidneys. No differences were noticed for local inflammatory responses, but serum CCL2 was significantly higher in WT versus Mcpt4(-/-) and W(sh/sh) mice. Alpha-smooth muscle actin (αSMA) expression, a marker of epithelial-mesenchymal transition (EMT), was high in WT, minimal for W(sh/sh), and intermediate for Mcpt4(-/-) RK. Supernatants of acti...Continue Reading

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Citations

Aug 3, 2018·Biological & Pharmaceutical Bulletin·Grasielle Lopes de Oliveira-SilvaLuiz Borges Bispo-da-Silva
Nov 1, 2017·Hypertension·Hadrien-Gaël BoyerEstelle Louiset
Dec 6, 2018·Frontiers in Immunology·Flavie Ngo NyekelGregory Gautier
Sep 23, 2020·Nature Reviews. Nephrology·David A C MessererMarkus Huber-Lang
Feb 13, 2018·Immunological Reviews·Barbara FrossiCarlo E M Pucillo
Dec 25, 2019·Physiological Reports·Benjamin J BivonaLisa M Harrison-Bernard
Jan 6, 2021·International Journal of Molecular Sciences·Shamila VibhushanUlrich Blank

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Methods Mentioned

BETA
transgenic
dissection
electrophoresis
ELISA
biopsy

Software Mentioned

GraphPad Prism
ImageScope
GraphPad
ImageJ
NIH
NIH ImageJ

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