Nephropathogenic infectious bronchitis virus induces epithelial-mesenchymal transition of renal tubular epithelial cells through the TGF-β/p-P38 pathway causing uric acid excretion disorder in chickens.

Abstract

Nephropathogenic infectious bronchitis virus (NIBV) infection usually causes kidney enlargement and urate deposition in chickens, leading to sudden death. However, the mechanism by which NIBV causes urate deposition in the kidneys has not yet been elucidated. The coordinated operation of uric acid transporters is crucial for the kidneys to maintain uric acid homeostasis, and existing studies have shown that the occurrence of cell epithelial-mesenchymal transition (EMT) can affect the expression of uric acid transporters. Thus, this study aimed to explore the effect of NIBV on urate transporters and elucidate the mechanism of EMT in NIBV-induced urate deposition in chicken kidneys in vivo and in vitro. The results revealed that NIBV infection led to an abnormal increase in uric acid levels in chicks, affected the expression of uric acid transport proteins, induced EMT in renal tubular epithelial cells, and activated the TGF-β/p-p38 pathway. The changes in uric acid concentration induced by NIBV were related to the uric acid excretion protein ABCG2, whose expression is negatively regulated by EMT. The occurrence of NIBV-induced EMT coincided with the time point at which NIBV activated the TGF-β/p-p38 pathway. After siRNA knockdown of p38 MAPK, EMT did not occur, and ABCG2 expression returned to normal. In summary, the mechanism by which NIBV causes abnormal elevation of uric acid levels in chickens is through the induction of EMT in renal tubular epithelial cells via the TGF-β/p-p38 pathway, which strongly inhibits the expression of ABCG2, thereby causing uric acid excretion disorders in chickens.IMPORTANCENIBV infection results in a reduction in uric acid transporter expression in the kidneys of chickens. ABCG2 plays a pivotal role in the excretion of uric acid in chickens. The mechanism by which NIBV causes an abnormal increase in uric acid levels in chickens involves the induction of renal tubular epithelial cell EMT through the TGF-β/P-p38 pathway and the subsequent strong inhibition of ABCG2 expression, causing uric acid excretion disorders in chickens.