title: Reduced NOV/CCN3 Expression Limits Inflammation and Interstitial Renal Fibrosis after Obstructive Nephropathy in Mice.
abstract: The main hallmark of chronic kidney disease (CKD) is excessive inflammation leading to interstitial tissue fibrosis. It has been recently reported that NOV/CCN3 could be involved in kidney damage but its role in the progression of nephropathies is poorly known. NOV/CCN3 is a secreted multifunctional protein belonging to the CCN family involved in different physiological and pathological processes such as angiogenesis, inflammation and cancers. The purpose of our study was to determine the role of NOV/CCN3 in renal inflammation and fibrosis related to primitive tubulointerstitial injury. After unilateral ureteral obstruction (UUO), renal histology and real-time PCR were performed in NOV/CCN3-/- and wild type mice. NOV/CCN3 mRNA expression was increased in the obstructed kidneys in the early stages of the obstructive nephropathy. Interestingly, plasmatic levels of NOV/CCN3 were strongly induced after 7 days of UUO and the injection of recombinant NOV/CCN3 protein in healthy mice significantly increased CCL2 mRNA levels. Furthermore, after 7 days of UUO NOV/CCN3-/- mice displayed reduced proinflammatory cytokines and adhesion markers expression leading to restricted accumulation of interstitial monocytes, in comparison with their wild type littermates. Consequently, in NOV/CCN3-/- mice interstitial renal fibrosis was blunted after 15 days of UUO. In agreement with our experimental data, NOV/CCN3 expression was highly increased in biopsies of patients with tubulointerstitial nephritis. Thus, the inhibition of NOV/CCN3 may represent a novel target for the progression of renal diseases.
authors.affiliation: INSERM, UMR-S938, Centre de Recherche Saint-Antoine, Saint-Antoine Hospital, Paris, France; INSERM UMR-S1155, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France.
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Marchal
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kavvadas
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abed
authors.affiliation: INSERM, UMR-S938, Centre de Recherche Saint-Antoine, Saint-Antoine Hospital, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Kazazian
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Authier
authors.affiliation: RIKEN Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Department of Biochemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hiraoka
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France; Department of Nephrology, Tenon Hospital, Paris, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Boffa
authors.affiliation: INSERM, UMR-S938, Centre de Recherche Saint-Antoine, Saint-Antoine Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Martinerie
authors.affiliation: INSERM UMR-S1155, Tenon Hospital, Paris, France; Sorbonne Universités, UPMC Univ Paris 6, Paris, France.
authors.forename: Christos E
authors.initials: CE
authors.lastname: Chadjichristos
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009395:Nephritis, Interstitial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055514:Nephroblastoma Overexpressed Protein / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000473:pathology; D014517:Ureteral Obstruction / Q000378:metabolism
chemical_list: D015415:Biomarkers; C526319:CCN3 protein, human; C526320:Ccn3 protein, mouse; D055514:Nephroblastoma Overexpressed Protein