TNF-alpha-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-kappaB Signaling in Kidney Tubular Cells #MMPMID28821873
Lee HH; Cho YI; Kim SY; Yoon YE; Kim KS; Hong SJ; Han WK
Sci Rep 2017[Aug]; 7 (1): 8856 PMID28821873show ga
Apo-A4 expression was increased in tissues from chronic kidney disease (CKD) patients compared to that in normal kidney tissue. We determined the association of apo-A4 and its regulatory signals following acute kidney injury and elucidated the effects of apo-A4 on cell signaling pathways related to kidney injury in vitro and in vivo. Tumor necrosis factor (TNF)-alpha, which causes inflammatory cell injury, induced significantly increased expression of apo-A4 protein levels, and these levels were related to pro-inflammatory acute kidney injury in human kidney cells. Apo-A4 expression was also increased in experimented rat kidney tissues after ischemic reperfusion injury. The expression of tumor necrosis factor receptor (TNFR) 2 was increased in both kidney cell lines and experimented rat kidney tissues following acute kidney injury. The expression of apo-A4 and TNFR2 was increased upon treatment with TNF-alpha. Immunohistochemistry revealed positive apo-A4 and TNFR2 staining in ischemic reperfusion injury rat kidneys compared with levels in the sham operation kidneys. After neutralization of TNF-alpha, NF-kappaB expression was only observed in the cytoplasm by immunofluorescence. Therefore, the apo-A4 expression is increased by stimulation of injured kidney cells with TNF-alpha and that these effects occur via a TNFR2-NFkappaB complex.
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Sci+Rep 2017 ; 7 (1): 8856
