Frontiers in Immunology (May 2017)
Mast Cells and MCPT4 Chymase Promote Renal Impairment after Partial Ureteral Obstruction
- Maguelonne Pons,
- Maguelonne Pons,
- Maguelonne Pons,
- Maguelonne Pons,
- Liza Ali,
- Liza Ali,
- Liza Ali,
- Liza Ali,
- Walid Beghdadi,
- Walid Beghdadi,
- Walid Beghdadi,
- Luca Danelli,
- Luca Danelli,
- Marianne Alison,
- Lydia Celia Madjène,
- Lydia Celia Madjène,
- Lydia Celia Madjène,
- Jessica Calvo,
- Julien Claver,
- Julien Claver,
- Julien Claver,
- Shamila Vibhushan,
- Shamila Vibhushan,
- Shamila Vibhushan,
- Magnus Åbrink,
- Gunnar Pejler,
- Gunnar Pejler,
- Marie-Laurence Poli-Mérol,
- Michel Peuchmaur,
- Alaa El Ghoneimi,
- Alaa El Ghoneimi,
- Alaa El Ghoneimi,
- Alaa El Ghoneimi,
- Ulrich Blank,
- Ulrich Blank,
- Ulrich Blank
Affiliations
- Maguelonne Pons
- INSERM UMRS 1149, Paris, France
- Maguelonne Pons
- CNRS ERL8252, Paris, France
- Maguelonne Pons
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Maguelonne Pons
- Department of Pediatric Surgery and Urology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Liza Ali
- INSERM UMRS 1149, Paris, France
- Liza Ali
- CNRS ERL8252, Paris, France
- Liza Ali
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Liza Ali
- Department of Pediatric Surgery and Urology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Walid Beghdadi
- INSERM UMRS 1149, Paris, France
- Walid Beghdadi
- CNRS ERL8252, Paris, France
- Walid Beghdadi
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Luca Danelli
- CNRS ERL8252, Paris, France
- Luca Danelli
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Marianne Alison
- Department of Pediatric Radiology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Lydia Celia Madjène
- INSERM UMRS 1149, Paris, France
- Lydia Celia Madjène
- CNRS ERL8252, Paris, France
- Lydia Celia Madjène
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Jessica Calvo
- Department of Pathology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Julien Claver
- INSERM UMRS 1149, Paris, France
- Julien Claver
- CNRS ERL8252, Paris, France
- Julien Claver
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Shamila Vibhushan
- INSERM UMRS 1149, Paris, France
- Shamila Vibhushan
- CNRS ERL8252, Paris, France
- Shamila Vibhushan
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Magnus Åbrink
- Section of Immunology, Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden
- Gunnar Pejler
- Uppsala University, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden
- Gunnar Pejler
- Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden
- Marie-Laurence Poli-Mérol
- 0Pediatric Surgery Unit, American Memorial Hospital, Université Reims Champagne Ardennes, Reims, France
- Michel Peuchmaur
- Department of Pathology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Alaa El Ghoneimi
- INSERM UMRS 1149, Paris, France
- Alaa El Ghoneimi
- CNRS ERL8252, Paris, France
- Alaa El Ghoneimi
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- Alaa El Ghoneimi
- Department of Pediatric Surgery and Urology, Hôpital Robert Debré, APHP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France
- Ulrich Blank
- INSERM UMRS 1149, Paris, France
- Ulrich Blank
- CNRS ERL8252, Paris, France
- Ulrich Blank
- Université Paris Diderot, Sorbonne Paris Cité, Laboratoire d’excellence INFLAMEX, Paris, France
- DOI
- https://doi.org/10.3389/fimmu.2017.00450
- Journal volume & issue
-
Vol. 8
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- (Wsh/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 Wsh/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 Wsh/sh mice. Alpha-smooth muscle actin (αSMA) expression, a marker of epithelial–mesenchymal transition (EMT), was high in WT, minimal for Wsh/sh, and intermediate for Mcpt4−/− RK. Supernatants of activated MC induced αSMA in co-culture experiments with proximal tubular epithelial cells. Our results support a role of MC in EMT and parenchyma lesions after pUUO involving, at least partly, MCPT4 chymase. They confirm the importance of morphologic impairment evaluation by MRI in pUUO.
Keywords
