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01-12-2014 | Original Article

Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor

Authors: Sho Ishizawa, Junko Takahashi-Fujigasaki, Yasushi Kanazawa, Keiichiro Matoba, Daiji Kawanami, Tamotsu Yokota, Takeo Iwamoto, Naoko Tajima, Yoshinobu Manome, Kazunori Utsunomiya

Published in: Clinical and Experimental Nephrology | Issue 6/2014

Abstract

Background

Sphingosine-1-phosphate (S1P) is reportedly involved in the pathogenesis of kidney disease; however, the precise role played by S1P in renal disorders still remains controversial. Rho kinase plays an important role in the development of diabetic nephropathy by inducing glomerular and tubulointerstitial fibrosis. Rho kinase is known to be stimulated by S1P through its specific receptor, S1P2 receptor (S1P2). Hence, we investigated whether S1P–S1P2 signaling plays a role in the epithelial–mesenchymal transition (EMT) through Rho kinase activation in renal tubules.

Method

To characterize the distribution of the S1P2, an immunohistochemical examination of the receptor was performed in the kidney of the non-diabetic and diabetic mice. Next, we examined Rho kinase activity as well as E-cadherin and alpha-smooth muscle actin (α-SMA) expression by real-time RT-PCR and western blotting in cultured rat tubular epithelial cells under S1P stimulation with and without a Rho kinase inhibitor and an S1P2 blocker. In addition, the distribution of E-cadherin and α-SMA was examined by immunocytochemistry.

Result

S1P2 was expressed mainly in the renal tubules; expression was intense in collecting ducts and distal tubules compared to other segments. S1P induced activation of Rho kinase through the S1P2, which changed the distribution of E-cadherin and increased the expression of α-SMA.

Conclusion

Rho kinase activation by S1P via S1P2 initiated EMT changes in cultured renal tubular cells. Our results suggest that excessive stimulation of S1P might facilitate renal fibrosis via activation of Rho kinase through S1P2.

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Title: Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor
Authors: Sho Ishizawa
Junko Takahashi-Fujigasaki
Yasushi Kanazawa
Keiichiro Matoba
Daiji Kawanami
Tamotsu Yokota
Takeo Iwamoto
Naoko Tajima
Yoshinobu Manome
Kazunori Utsunomiya
Publication date: 01-12-2014
Publisher: Springer Japan
Published in: Clinical and Experimental Nephrology / Issue 6/2014
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-014-0933-x

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Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor

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Result

Conclusion

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