Sphingosine 1-Phosphate Receptor 5 (S1P5) Knockout Ameliorates Adenine-Induced Nephropathy.

Abstract

S1P and its receptors have been reported to play important roles in the development of renal fibrosis. Although S1P5 has barely been investigated so far, there are indications that it can influence inflammatory and fibrotic processes. Here, we report the role of S1P5 in renal inflammation and fibrosis. Male S1P5 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 S1P5 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. S1P5 knockout ameliorates tubular damage and tubulointerstitial fibrosis in a model of adenine-induced nephropathy in mice. Thus, targeting S1P5 might be a promising goal for the pharmacological treatment of kidney diseases.

• Authors: Timon Eckes, Sammy Patyna, Alexander Koch, Anke Oftring, Stefan Gauer, Nicholas Obermüller, Stephanie Schwalm, Liliana Schaefer, Jerold Chun, Hermann-Josef Gröne, Josef Pfeilschifter
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 7 (Apr 02 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35409312 (Publication Type: Journal Article)

Chemical References

• Sphingosine-1-Phosphate Receptors
• Adenine
• Sphingosine

Topics

• Adenine (adverse effects)
• Animals
• Fibrosis
• Inflammation
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Renal Insufficiency, Chronic (pathology)
• Sphingosine (pharmacology)
• Sphingosine-1-Phosphate Receptors