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IL-17 Receptor Signaling Negatively Regulates the Development of Tubulointerstitial Fibrosis in the Kidney
Joint Authors
Ramani, Kritika
Tan, Roderick J.
Zhou, Dong
Coleman, Bianca M.
Jawale, Chetan V.
Biswas, Partha S.
Liu, Youhua
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-10-14
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Chronic inflammation has an important role in the development and progression of most fibrotic diseases, for which no effective treatments exist.
Tubulointerstitial fibrosis (TF) is characterized by irreversible deposition of fibrous tissue in chronic kidney diseases.
Prolonged injurious stimuli and chronic inflammation regulate downstream events that lead to TF.
In recent years, interleukin-17 (IL-17) has been strongly linked to organ fibrosis.
However, the role of IL-17 receptor signaling in TF is an active area of debate.
Using the unilateral ureteral obstruction (UUO) mouse model of TF, we show that IL-17 receptor A-deficient mice (Il17ra−/−) exhibit increased TF in the obstructed kidney.
Consequently, overexpression of IL-17 restored protection in mice with UUO.
Reduced renal expression of matrix-degrading enzymes results in failure to degrade ECM proteins, thus contributing to the exaggerated TF phenotype in Il17ra−/− mice.
We demonstrate that the antifibrotic kallikrein-kinin system (KKS) is activated in the obstructed kidney in an IL-17-dependent manner.
Accordingly, Il17ra−/− mice receiving bradykinin, the major end-product of KKS activation, prevents TF development by upregulating the expression of matrix-degrading enzymes.
Finally, we show that treatment with specific agonists for bradykinin receptor 1 or 2 confers renal protection against TF.
Overall, our results highlight an intriguing link between IL-17 and activation of KKS in protection against TF, the common final outcome of chronic kidney conditions leading to devastating end-stage renal diseases.
American Psychological Association (APA)
Ramani, Kritika& Tan, Roderick J.& Zhou, Dong& Coleman, Bianca M.& Jawale, Chetan V.& Liu, Youhua…[et al.]. 2018. IL-17 Receptor Signaling Negatively Regulates the Development of Tubulointerstitial Fibrosis in the Kidney. Mediators of Inflammation،Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1203845
Modern Language Association (MLA)
Ramani, Kritika…[et al.]. IL-17 Receptor Signaling Negatively Regulates the Development of Tubulointerstitial Fibrosis in the Kidney. Mediators of Inflammation No. 2018 (2018), pp.1-14.
https://search.emarefa.net/detail/BIM-1203845
American Medical Association (AMA)
Ramani, Kritika& Tan, Roderick J.& Zhou, Dong& Coleman, Bianca M.& Jawale, Chetan V.& Liu, Youhua…[et al.]. IL-17 Receptor Signaling Negatively Regulates the Development of Tubulointerstitial Fibrosis in the Kidney. Mediators of Inflammation. 2018. Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1203845
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203845