Follistatin-like 1 Prevents Renal Ischemia-Reperfusion Injury by Inhibition of Apoptosis via Upregulating AMPK/PPAR-δ Pathway

Abstract

Abstract Follistatin-like 1 (FSTL-1), a secreted glycoprotein, is upregulated in the serum of patients with acute kidney injury. However, it is unknown whether it protects against renal ischemia-reperfusion (I/R) injury. Our present study found that treatment with FSTL-1 (100 mg/kg) intravenous injection alleviated renal injury, as evidenced by reduced serum creatinine (Scr) and blood urea nitrogen (BUN) levels, along with reduced histopathological kidney damage. Moreover, FSTL-1 treatment reduced the number of apoptotic cells and the accumulation of reactive oxygen species (ROS) during I/R injury. The protective effect of FSTL-1 was via AMPK/PPAR-δ pathway, because, after blockade of AMPK/PPAR-δ pathway by individual inhibitor (GSK0660, a PPAR-δ antagonist, or compound C, an AMPK inhibitor), the protective effects of FSTL-1 on oxidative stress and apoptosis were blocked. Taken together, our results reveal that FSTL-1 attenuates renal I/R injury by inhibiting apoptosis in renal tubular epithelial cells, which is meditated by activating AMPK/PPAR-δ pathway.