| 초록 |
Objectives : Unilateral ureteral obstruction (UUO) induced mitochondrial dysfunction resulting in increase of oxidative stress and inflammation in obstructed kidney. Although mitochondria play a role in UUO injury including tubulo-interstitial apoptosis, inflammation and fibrosis, the role of collecting duct cells was not evaluated. We evaluated whether collecting duct specific mitochondrial dysfunction affect the renal injury induced by UUO.
Methods : For generation collecting duct specific mitochondrial injury mice, CRIF flox/flox mice were bred with Hoxb7-Cre mice. For evaluation of the phenotype of mice, we observed mitochondria using electron microscopy in mice. For evaluation of influence of CRIF1 deletion on mitochondrial function, we measured O2 consumption and membrane potential in control and silencing RNA treated mIMCD cells. For evaluation of effect on UUO induced renal injury, we divided mice into the following 4 groups: CRIF1flox/flox(WT) group; CRIF1 flox/flox-Hob7 Cre (CRIF1-KO) group; WT UUO group; and CRIF1-KO UUO group. I evaluated oxidative stress, inflammatory, and fibrosis marker in urine and kidney tissue.
Results : There are no significant diffenence in phenotype between CRIF1-KO and WT mice. Renal expression of MCP-1, osteopontin (OPN), Numbers of F4/80 positive cells, TGF-b, a-SMA, and Masson Trichrome stained area were significantly increased in CRIF1-KO-UUO kidneys compared with WT UUO kidneys., Urinary 8-OHDG was increased in CRIF1-KO-mice compared with WT mice. Also, Crif1-KO mice had significantly increase of 8-OHDG-positive cell recruitment compared to WT mice. CRIF1-KO-UUO-kidneys were shown more increase recruitment of 8-OHDG-positive cells compared to WT UUOkindneys
Conclusions : Collecting duct specific mitochondrial injury induced increase of oxidative stress, renal inflammation, and renal fibrosis in UUO mice |