Short-Term Activation of Hypoxia-Inducible Factor Slows Kidney Disease Progression in Rat Model of 5/6 ;Subtotal Nephrectomy by Up-regulating MiR-29c Expression
- VernacularTitle:低氧诱导因子短期活化后诱导 miR-29c表达上调可延缓5／6肾切除大鼠的肾病进展
- Author:
Yiran LIANG
1
;
Yanyan HENG
;
Ang Xiaof YU
;
Ping JIA
;
Yi NG FA
Author Information
1. 复旦大学附属中山医院肾内科
- Keywords:
MiR-29c;
Renal tubulointerstitial fibrosis;
Hypoxia-inducible factor;
Tropomyosin-1
- From:
Chinese Journal of Clinical Medicine
2016;23(1):6-12
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and probable mechanism of moderate activation of hypoxia‐inducible factor(HIF) in slowing chronic kidney disease progression of remnant kidney .Methods :Rat models of remnant kidney were established by 5/6 subtotal nephrectomy in male Sprague‐Dawley rats . And then they were randomly allocated to L‐mimosine (L‐Mim ) treatment group ,in which the rats were treated with intraperitoneal injections of L‐Mim during 5‐12 week after operation ,and untreated remnant kidney group .Meanwhile ,sham operated rats were set as control group .All rats were sacrificed at the end of week 12 ,and the specimens were collected .Results:The serum creatinine level in L‐Mim treatment group was lower than that in untreated remnant kidney group(82 .4 ± 6 .3 vs .130 .1 ± 24 .1 μmol/L ,P<0 .05) ,as well as the 24 h Ualb level (0 .7 ± 0 .1 vs .1 .7 ± 0 .5 g/d , P< 0 .05) .And the pathological changes in in L‐Mim treatment group was slightly improved while compared to untreated remnant kidney group .The result of miRNA microarray analysis showed that miR‐29c in renal cortex was up‐regulated in L‐Mim group compared with untreated remnant group and meanwhile the expressions of HIF‐1αand HIF‐2αincreased .Tropomyosin 1 (TPM1) met the sequence criteria for microRNA‐target interaction ,which was later confirmed by luciferase reporter system and mutation test in vitro .HK2 cell transfected with pre‐miT‐29c oligonucleotide could inhibit the tropomyosin up‐regulation induced by TGF‐β1 treatment (3 ng/mL ,24 h) , P<0 .05 or 0 .01 .Conclusions :Renal interstitial fibrosis in rat remnant kidney was significant ,and it was accompanied by the miR‐29c down‐regulation .Moderate activation of HIF level may attenuate the deterioration of renal function by up‐regulating miR‐29c expression .
