TNF-α induced pro-inflammation stimulates apolipoprotein-A4 via activation of a TNFR2 and NF-κB signaling pathway in kidney tubular cell

Abstract

Acute kidney injury (AKI) is the initial stage of kidney disease and can lead to chronic kidney disease (CKD). Human apolipoprotein A4 (apo-A4) levels are significantly elevated in early-stage CKD. Moreover, elevated apo-A4 levels in the kidney lead to abnormal apo-A4 protein deposits in body tissues and organs, which can cause amyloidosis. Therefore, apo-A4 regulation can affect cell viability following kidney injury. To determine which types of AKI affect apo-A4 levels, we induced AKI in human kidney cells using a variety of conditions. Apo-A4 expression level was only affected by Tumor necrosis factor alpha (TNF-α) treatment. Our data showed that pro-inflammatory AKI caused by TNF-α induced TNFR2 activation via NF-ĸB and enhanced apo-A4 expression in human kidney cells and tissues. Moreover, apo-a4 overexpression affected the recovery of kidney cells. In conclusion, apo-A4 expression was upregulated by TNF-α. In addition, we showed that inflammatory kidney damage occurs through a TNFR2-NFĸB complex and that apo-A4 regulation can affect cell viability