Sphingosine 1-Phosphate Receptor 5 (S1P 5 ) Knockout Ameliorates Adenine-Induced Nephropathy.

S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P 5 has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P 5 in renal inflammation and fibrosis. Male S1P 5 knockout mice and wild-type mice on a C57BL/6J background were fed with an adenine-rich diet for 7 days or 14 days to induce tubulointerstitial fibrosis. The kidneys of untreated mice served as respective controls. Kidney damage, fibrosis, and inflammation in kidney tissues were analyzed by real-time PCR, Western blot, and histological staining. Renal function was assessed by plasma creatinine ELISA. The S1P 5 knockout mice had better renal function and showed less kidney damage, less proinflammatory cytokine release, and less fibrosis after 7 days and 14 days of an adenine-rich diet compared to wild-type mice. S1P 5 knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P 5 might be a promising goal for the pharmacological treatment of kidney diseases.