Periostin Induces Kidney Fibrosis after Acute Kidney Injury via p38 MAPK pathway

Abstract

Background: Periostin, a matricellular protein, has been reported to play a crucial role in fibrosis. Acute kidney injury results in a high risk of progression to chronic kidney disease. It was hypothesized that periostin is involved in the progression of acute kidney injury to kidney fibrosis. Methods: Unilateral ischemia-reperfusion injury using 7- to 8-week-old male wild-type and periostin null mice was induced and the animals were observed for 6 weeks. In vitro, human kidney-2 cells were subjected to a hypoxic incubator (5% O2, 5% CO2, and 90% N2) for 24 hours and 5 days. The cells were also cultured with a p38 mitogen-activated protein kinase (MAPK) inhibitor in the hypoxic incubator for 5 days. Results: At 6 weeks after induction of unilateral ischemia-reperfusion injury, the kidneys in periostin null mice were less atrophied, and interstitial fibrosis/tubular atrophy was significantly alleviated in periostin null mice compared with those in wild-type mice. The expressions of phosphorylated-p38 MAPK were also decreased in periostin null mice compared to those in wild-type mice. Furthermore, periostin null mice had attenuated mRNA and protein expression of fibrosis and apoptosis markers. In vitro, hypoxic injury (5% O2, 5% CO2, and 90% N2) of the human kidney-2 cells for 24 hours and 5 days increased the expressions of phosphorylated-p38 MAPK and fibrosis markers. Recombinant periostin in hypoxic conditions enhanced phosphorylated-p38 MAPK expression, which was comparable to that with recombinant transforming growth factor-β1. In contrast, inhibition of p38 MAPK ameliorated hypoxia-induced fibrosis. Conclusion: In conclusion, periostin promotes kidney fibrosis via the p38 MAPK pathway following acute kidney injury triggered by hypoxic or ischemic insult. Periostin ablation could protect against kidney progression.