Role of SphK1 in renal tubulointerstitial fibrosis and its mechanism
10.3969/j.issn.1001-1978.2017.02.014
- VernacularTitle:鞘氨醇激酶1在肾间质纤维化中的作用及机制研究
- Author:
Chunyang DU
;
Xia XIAO
;
Xingui WANG
;
Jiao FU
;
Yiping FENG
;
Fengli HU
;
Enli CHEN
;
Yunzhuo REN
- Keywords:
sphingosine kinase 1;
unilateral ureteral obstruction;
autophagy;
fibrosis;
PF-543;
transmission e-lectron microscope
- From:
Chinese Pharmacological Bulletin
2017;33(2):212-217,218
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.
