In:
Acta Physiologica, Wiley, Vol. 226, No. 2 ( 2019-06)
Kurzfassung:
Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin‐1, a member of the interleukin‐6 family of cytokines, protects several organs from damage by promoting survival and anti‐inflammatory effects. However, whether cardiotrophin‐1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. Methods We hypothesized and assessed the potential role of cardiotrophin‐1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). Results Three days after UUO, obstructed kidneys from cardiotrophin‐1 −/− mice show higher expression of inflammatory markers IL‐1β, Cd68, ICAM‐1, COX‐2 and iNOs, higher activation of NF‐κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild‐type littermates. In a later stage, obstructed kidneys from cardiotrophin‐1 −/− mice show higher fibrosis than obstructed kidneys from wild‐type mice. Interestingly, administration of exogenous cardiotrophin‐1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin‐1 upon UUO, and supplementation of wild‐type mice with exogenous cardiotrophin‐1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin‐1 −/− mice have higher collagen I and fibronectin expression and higher NF‐κB activation than wild‐type cells. Conclusions Cardiotrophin‐1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin‐1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis.
Materialart:
Online-Ressource
ISSN:
1748-1708
,
1748-1716
DOI:
10.1111/apha.2019.226.issue-2
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2019
ZDB Id:
2617148-X
ZDB Id:
2219379-0
SSG:
12
