Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i.

Abstract:

:The epithelial-mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGFβ and NFκB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGFβ in polycystic kidney disease and attenuate EMT in renal tubular cells. Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes through downregulating the expression and activation of TGFβ/Smad pathway in diabetic kidney diseases. The results showed that apelin in glomeruli of diabetic mice were increased and exogenous apelin inhibited the EMT of podocytes in diabetic mice, which were accompanied with the decreased expression of proteasome subunits β5i. The results from β5iKO mice confirmed that the inhibiting effects of apelin on EMT of podocytes in diabetic mice were dependent on β5i. The results from culture podocytes showed that apelin decreased the degradation of pIκB and promoted the translocation of IκB into nucleus through decreasing the expression of β5i, which would inhibit the promoting effects of NFκB on expression of TGFβ and followed by decreased activation of Smad pathway and EMT in podocytes. In conclusion, apelin might act as an EMT suppressor for podocytes to decrease the process of glomerular fibrosis in diabetic mice.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Yin J,Wang Y,Chang J,Li B,Zhang J,Liu Y,Lai S,Jiang Y,Li H,Zeng X

doi

10.1038/s41419-018-1098-4

subject

Has Abstract

pub_date

2018-10-09 00:00:00

pages

1031

issue

10

issn

2041-4889

pii

10.1038/s41419-018-1098-4

journal_volume

9

pub_type

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