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Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage.
- Source :
-
Cellular Physiology & Biochemistry (Karger AG) . Jul2015, Vol. 36 Issue 4, p1274-1290. 17p. - Publication Year :
- 2015
-
Abstract
- Background/Aims: Although the disturbance of T lymphocyte and glomerular podocyte exerts a crucial function in the pathogenesis of proteinuria, the potential link is still unclear. Methods: The balance of Treg and Th17 cells, and the expression of IL-17/IL-17R and c-mip were investigated in adrimycin-induced nephropathy (AN) mice. The effect and mechanism of IL-17 on podocyte were explored in cultured podocytes. Results: The proportion of Th17 cells in peripheral blood mononuclear cells, the amount of IL-17 in serum and kidney cortical homogenates, and the expression of IL-17R and c-mip in glomerular podocyte were increased obviously in AN mice. In cultured podocytes, recombinant IL-17 led to an induction of apoptosis and cytoskeletal disorganization, an overproduction of c-mip while downregulation of phosphor-nephrin, and an increased binding of c-mip to NF-KB/RelA. Silence of c-mip prevented podocyte apoptosis and reduction of phosphor-nephrin by prompting nuclear translocation of NF-KB/RelA in IL-17 treated cells. Persistent activation of NF-KB upregulated pro-survival protein Bcl-2 and decreased podocyte apoptosis, but had no effect on phosphor-nephrin level. Conclusion: These findings demonstrated that induction of IL-17 released by Th17 cells plays a key role in podocytopathy most likely through down-regulation of phosphor-nephrin and Bcl-2 level via overproduction of c-mip. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10158987
- Volume :
- 36
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Cellular Physiology & Biochemistry (Karger AG)
- Publication Type :
- Academic Journal
- Accession number :
- 108397218
- Full Text :
- https://doi.org/10.1159/000430296