Revue d'histoire du Bas-Saint-Laurent, vol. 17 (2)

Éditorial -- Les familles souches de Squatec -- La polyvalente de Squatec: vingt-cinq ans d'histoire 1969-1994 -- Matamajaw Salmon Club -- La pêche à l'anguille sur la Côte-du-Sud -- Saint-Narcisse-de-Rimouski, hier et aujourd'hui -- Quand les curés s'arrachaient les colons: le cas de l'abbé Antoine-Philippe Bérubé -- Le club Leblanc des Eaux Mortes -- Chroniques rimouskoises -- James-J. Jessop (1892-1939): avocat et maire de Rimouski -- Patrimoine: Une tournée historique: le patrimoine architectural de la région de Rivière-du-Loup -- Maison Hamel: la petite histoire d'une rimouskoise plus que centenaire -- La maison Gauvreau: une sauvegarde difficile -- Folklore: Naufrage du trois-mâts Amanda à Petit-Métis en 1841 -- On en fait toute une histoire au Musée du Bas-Saint-Laurent -- Paul Triquet, les 50 ans de sa croix Victoria -- En bref -- Des livres à lire

Reduced NOV/CCN3 Expression Limits Inflammation and Interstitial Renal Fibrosis after Obstructive Nephropathy in Mice

International audienceThe 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

NOV expression in human tubulointerstitial nephritis.

<p>(A), (B), (C) and (D) Representative immunostainings of human biopsies showed a glomerular expression of NOV in healthy kidneys (A and B). Tubulointerstitial nephritis induced a de novo expression of NOV within the tubulointerstitial compartment (C and D). Magnification X400 (A, B and C) and X200 (D).</p

F4/80 expression in absence of NOV after 7 days of UUO.

<p>(A) Immunostaining and (B) quantification showed a marked increase of F4/80 protein expression after 7 days of UUO in WT. In Nov-/-, the upregulation of F4/80 was significantly restricted. Values are means ± SEM expressed as arbitrary units. n = 3 for ctrl, 9 for WT UUO and 7 for NOV-/- UUO. *<i>P</i><0.05, UUO vs. ctrl. Magnification X200 (A).</p

NOV expression in renal cortex and plasma after UUO.

<p>(A) RT-qPCR analysis in the renal cortex showed increased expression of NOV mRNA after 3, 7 and 15 days of UUO compared to contralateral cortex. Values are means ± SEM and expressed as the ratio of the target gene to the internal control gene (S26 rRNA). n = 7 for each group. *<i>P</i><0.05 and ***<i>P</i><0.001, UUO vs. ctrl, #P<0.05, WT ctrl versus Nov-/- ctrl. (B) Quantification of NOV concentration by ELISA showed an increased expression of NOV in plasma after 7 days of UUO compared to sham mice. Values are means ± SEM in ng/mL. n = 9 for sham animals and 4 for both UUO time points. ***<i>P</i> <0.001, UUO vs. sham.</p

Primers sequences.

<p>Primers sequences.</p

Inflammatory markers expression after injection of NOV recombinant protein and/or in absence of NOV after 3 days of UUO.

<p>(A) qPCR analysis in the renal cortex showed increased expression of CCL2 mRNA 24h after injection of NOV recombinant protein (50μg/mouse) compared to mice injected with vehicle. n = 4 for each group. **<i>P</i><0.01, NOV treated mice vs. vehicle. (B), (C), (D) and (E) qPCR analysis in the renal cortex showed a marked increase of CCL2 (B), VCAM-1 (C), IL6 (D) and CD68 (E) mRNAs expression after 3 days of UUO in WT. In Nov-/-, upregulation of the above mentioned molecules was significantly restricted. Values are means ± SEM and expressed as the ratio of the target gene to the internal control gene (S26 rRNA). n = 9 for WT and 6 for NOV-/-. *<i>P</i><0.05, **<i>P</i><0.01 and ***<i>P</i><0.001, UUO vs. ctrl. (F) (G) Representative western blots for VCAM-1 and GAPDH were performed by using renal cortex of contralateral controls and obstructed kidneys from WT and NOV-/- mice. Graphs show quantification of western blots expressed as the ratio of VCAM-1 versus GAPDH signal for each sample (G).</p