Role of P311 in interleukin-1α-induced epithelial to myofibroblast transition in kidney tubular epithelial cells.
Tubular epithelial-myofibroblast transition (TEMT) is an important process in renal tubulointerstitial fibrosis. Interleukin-1α (IL-1α) and transforming growth factor-β1 (TGF-β1) have been demonstrated to be key inducers of TEMT. In mouse embryonic fibroblast cells (NIH3T3), P311 protein induces phenotypic changes that are consistent to myofibroblast transformation. In the present study, we investigated the role of P311 gene and protein as well as potential mechanisms underlying TEMT in normal rat kidney tubular epithelial cells (NRK52E). Morphological and molecular changes were determined in NRK52E cells that were treated with IL-1α and/or P311 antibodies. The results showed that the NRK52E cells triggered by IL-1α became fibroblast-like cells, exhibiting hypertrophy of elongated and fusiform-shaped cells. IL-1α induced a time-dependent increase in P311 gene expression in NRK52E cells, with a peak time at 4 days. The expression levels of P311 gene were positively correlated with α-SMA and TGF-β1 gene expression levels. Anti-P311 antibody inhibited P311 and α-SMA expression in the presence of IL-1α. In contrast, anti-P311 antibody increased the expression of TGF-β1 gene in cells cultured with IL-1α. Therefore, P311 gene, together with α-SMA and TGF-β1 genes, was induced in the process of TEMT. P311 protein triggered by interleukin-1α may promote TEMT through a TGF-β1-independent pathway.
a Department of Nephrology , Affiliated Hospital of Jining Medical University, Jining , Shandong , China .
Yiming
Y
Zhang
a Department of Nephrology , Affiliated Hospital of Jining Medical University, Jining , Shandong , China .
Xiaofen
X
Ma
b Department of Nephrology , Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) , Nanchong , Sichuan , China .
Xisheng
X
Xie
c Department of Pediatrics , Affiliated Hospital of Jining Medical University, Jining , Shandong , China .
Guangfei
G
Sun
a Department of Nephrology , Affiliated Hospital of Jining Medical University, Jining , Shandong , China .
Weidong
W
Liang
a Department of Nephrology , Affiliated Hospital of Jining Medical University, Jining , Shandong , China .
Xinjian
X
Li
d Department of Nephrology , Chengdu First People Hospital , Chengdu , Sichuan , China .
Fengping
F
Wang
e Department of Nephrology , Henan Provincial People Hospital, Zhengzhou , Henan , China .
Lina
L
Zhang
f Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment , Affiliated Hospital of Jining Medical University , Jining , Shandong , China , and.
Bo
B
Yan
g Department of Nephrology , Affiliated Hospital of Si Chuan Medical University, Luzhou , Sichuan , China.
Junming
J
Fan
D000199:Actins / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000648:ultrastructure*; D053582:Interleukin-1alpha / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D051379:Mice; D058628:Myofibroblasts / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000276:immunology; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
D000199:Actins; D053582:Interleukin-1alpha; D009419:Nerve Tissue Proteins; D053773:Transforming Growth Factor beta1; C497578:Nrep protein, rat; C498862:Acta2 protein, rat
P311; interleukin-1α; transforming growth factor-β1; tubular epithelial-myofibroblast transition; α-Smooth muscle actin