scholarly journals Vitamin D3 and erythropoietin protect against renal ischemia-reperfusion injury via heat shock protein 70 and microRNA-21 expression

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mohammad Ghasem Golmohammadi ◽  
Shokofeh Banaei ◽  
Kazem Nejati ◽  
Mir Mehdi Chinifroush-Asl

AbstractKidney ischemia reperfusion (IR) contributes to the development of acute kidney injury. The hypoxic conditions in ischemic damage lead to oxidative stress and apoptotic cell death. We investigated the effects of vitamin D3 (Vit D) and erythropoietin (EPO) on microRNA-21(miR-21) expression in renal IR. Wistar rats were divided into five groups including the control, vehicle + IR, Vit D + IR, EPO + IR, and Vit D + EPO + IR groups. The animals were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Vitamin D3 and EPO were administered prior to ischemia. After 24 h reperfusion, the kidney samples were collected for the detection of miR-21, heat shock protein 70 (hsp70) and caspase-3 expression levels. Kidney IR significantly increased the expression of miR-21, hsp70 and capase-3 and blood urea nitrogen (BUN)-Cr levels. Treatment with vitamin D3 and EPO significantly decreased the BUN-Cr levels and hsp70 and caspase-3 expression. Also, the co-administration of two drugs significantly increased miR-21 expression. It seems that vitamin D3 or EPO administration could protect the kidney against IR injury. However, vitamin D3 and EPO co-treatment was the most effective compared with the other treatment groups.

1999 ◽  
Vol 67 (5) ◽  
pp. 1421-1427 ◽  
Author(s):  
Masafumi Hiratsuka ◽  
Bassem N Mora ◽  
Motoki Yano ◽  
Thalachallour Mohanakumar ◽  
G.Alexander Patterson

Circulation ◽  
2001 ◽  
Vol 104 (suppl 1) ◽  
pp. I-303-I-307 ◽  
Author(s):  
Jay Jayakumar ◽  
Ken Suzuki ◽  
Ivan A. Sammut ◽  
Ryszard T. Smolenski ◽  
Mak Khan ◽  
...  

2009 ◽  
Vol 297 (4) ◽  
pp. F1109-F1118 ◽  
Author(s):  
Hsi-Hsien Chen ◽  
Tzen-Wen Chen ◽  
Heng Lin

Prostacyclin and peroxisome proliferator-activated receptors (PPAR) protect against ischemia-reperfusion (I/R) injury by the induction of an anti-inflammatory pathway. In this study, we examined the prostacyclin-enhanced protective effect of PPARα in I/R-induced kidney injury. PPAR-α reduced the NF-κB-induced overexpression of TNF-α and apoptosis in cultured kidney cells. In a murine model, pretreating wild-type (WT) mice with a PPAR-α activator, docosahexaenoic acid (DHA), significantly reduced I/R-induced renal dysfunction (lowered serum creatinine and urea nitrogen levels), apoptotic responses (decreased apoptotic cell number and caspase-3, -8 activation), and NF-κB activation. By comparison, I/R-induced injury was exacerbated in PPAR-α knockout mice. This indicated that PPAR-α attenuated renal I/R injury via NF-κB-induced TNF-α overexpression. Overexpression of prostacyclin using an adenovirus could also induce PPAR-α translocation from the cytosol into the nucleus to inhibit caspase-3 activation. This prostacyclin/PPAR-α pathway attenuated TNF-α promoter activity by binding to NF-κB. Using a cAMP inhibitor (CAY10441) and a prostacyclin receptor antibody, we also found that there was another prostacyclin/IP receptor/cAMP pathway that could inhibit TNF-α production. Taken together, our results demonstrate for the first time that prostacyclin induces the translocation of PPAR-α from the cytosol into the nucleus and attenuates NF-κB-induced TNF-α activation following renal I/R injury. Treatments that can augment prostacyclin, PPAR-α, or the associated signaling pathways may ameliorate conditions associated with renal I/R injury.


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