Effect of erythropoietin on the expression of dynamin-related protein-1 in rat renal interstitial fibrosis

Zhao,Xian‑Feng; Liu,Yan‑Hong; Han,Zi‑Ming; Xu,Yu

doi:10.3892/etm.2015.2419

Effect of erythropoietin on the expression of dynamin-related protein-1 in rat renal interstitial fibrosis

Authors:
- Xian‑Feng Zhao
- Yan‑Hong Liu
- Zi‑Ming Han
- Yu Xu
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Affiliations: Department of Cardiovascular Medicine, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China, Department of Neonatology, Zhengzhou People's Hospital, Zhengzhou, Henan 450000, P.R. China, Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: April 9, 2015 https://doi.org/10.3892/etm.2015.2419
Pages: 2065-2071
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

This study aimed to observe the expression of dynamin‑related protein‑1 (Drp‑1) in the renal interstitium in a rat model of renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). In addition, the renoprotective effect of erythropoietin in this model was investigated. A total of 81 rats were randomly assigned to sham surgery, UUO model and treatment groups. Following surgery, the rats in the treatment group were subcutaneously administered erythropoietin at a dose of 3,000 IU/kg once a week until the time of sacrifice. Rats in the sham surgery and UUO model groups were administered an identical volume of normal saline. In each group, nine rats were chosen randomly for sacrifice on days 7, 14 and 21 after surgery for histological examination of renal tissue. Renal tissue specimens were examined by hematoxylin and eosin and Masson's trichrome staining. Immunohistochemical analysis was performed to determine the expression of Drp‑1 in the renal interstitium. Renal function damage, as evaluated by the measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) levels, was less severe in the treatment group compared with that in the model group at day 21 (P<0.01). Compared with the UUO model group, the renal interstitial injury score and fibrotic area of the treatment group were decreased markedly at the three time points (P<0.05). The expression level of Drp‑1 in the treatment group was decreased markedly at the three time points compared with that in the model group (P<0.05). In conclusion, the expression of Drp‑1 is increased in rat renal interstitial fibrosis, and erythropoietin may alleviate the degree of renal interstitial fibrosis by downregulating the expression of Drp‑1.

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1	Nangaku M: Mechanisms of tubulointerstitial injury in the kidney: final common pathways to end-stage renal failure. Intern Med. 43:9–17. 2004. View Article : Google Scholar : PubMed/NCBI
2	Campanholle G, Ligresti G, Gharib SA and Duffield JS: Cellular mechanisms of tissue fibrosis 3. Novel mechanisms of kidney fibrosis. Am J Physiol Cell Physiol. 304:C591–C603. 2013. View Article : Google Scholar : PubMed/NCBI
3	Eddy AA: Molecular basis of renal fibrosis. Pediatric Nephrol. 15:290–301. 2000. View Article : Google Scholar
4	Ucero AC, Benito-Martin A, Izquierdo MC, et al: Unilateral ureteral obstruction: beyond obstruction. Int Urol Nephrol. 46:765–776. 2014. View Article : Google Scholar : PubMed/NCBI
5	Strutz F: Pathogenesis of tubulointerstitial fibrosis in chronic allograft dysfunction. Clin Transplant. 23 (Suppl 21):26–32. 2009. View Article : Google Scholar : PubMed/NCBI
6	Ucero AC, Goncalves S, Benito-Martin A, et al: Obstructive renal injury: from fluid mechanics to molecular cell biology. Open Access J Urol. 2:41–55. 2010.PubMed/NCBI
7	Otera H and Mihara K: Molecular mechanisms and physiologic functions of mitochondrial dynamics. J Biochem. 149:241–251. 2011. View Article : Google Scholar : PubMed/NCBI
8	Ucero AC, Benito-Martin A, Fuentes-Calvo I, et al: TNF-related weak inducer of apoptosis (TWEAK) promotes kidney fibrosis and Ras-dependent proliferation of cultured renal fibroblast. Biochim Biophys Acta. 1832:1744–1755. 2013. View Article : Google Scholar : PubMed/NCBI
9	Izquierdo MC, Sanz AB, Mezzano S, et al: TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int. 81:1098–1107. 2012. View Article : Google Scholar : PubMed/NCBI
10	Brines M and Cerami A: Discovering erythropoietin's extra-hematopoietic functions: biology and clinical promise. Kidney Int. 70:246–250. 2006. View Article : Google Scholar : PubMed/NCBI
11	Baker JE: Enythropoietin mimics ischemic preconditioning. Vascul Pharmacol. 42:233–241. 2005. View Article : Google Scholar : PubMed/NCBI
12	Chang YK, Choi DE, Na KR, et al: Erythropoietin attenuates renal injury in an experimental model of rat unilateral ureteral obstruction via anti-inflammatory and anti-apoptotic effects. J Urol. 181:1434–1443. 2009. View Article : Google Scholar : PubMed/NCBI
13	Cassis P, Gallon L, Benigni A, et al: Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury. Kidney Int. 81:903–918. 2012. View Article : Google Scholar : PubMed/NCBI
14	Yu XQ, Wu LL, Huang XR, et al: Osteopontin expression in progressive renal injury in remnant kidney:rule of angiotension II. Kidney Int. 58:1469–1480. 2000. View Article : Google Scholar : PubMed/NCBI
15	Li C, Chen Y and Hong MY: Erythropoietin protective effect of renal perfusion by pretreatment on acute global ischemia in rats. Zhongguo Bingli Shengli Zazhi. 20:2336–2338. 2004.
16	Srisawat N, Manotham K and Eiam-Ong S, Katavetin P, Praditpornsilpa K and Eiam-Ong S: Erythropoietin and its non-erythropoietic derivative: do they ameliorate renal tubulointerstitial injury in ureteral obstruction? Int J Urol. 15:1011–1017. 2008. View Article : Google Scholar : PubMed/NCBI
17	Sharples EJ, Patel N, Brown P, et al: Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. J Am Soc Nephrol. 15:2115–2124. 2004. View Article : Google Scholar : PubMed/NCBI
18	Ates E, Yalcin AU, et al: Protective effect of erythropoietin on renal ischemia and reperfusion injury. ANZ J Surg. 75:1100–1105. 2005. View Article : Google Scholar : PubMed/NCBI
19	Chevalier RL, Forbes MS and Thornhill BA: Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int. 75:1145–1152. 2009. View Article : Google Scholar : PubMed/NCBI
20	Pang M, Kothapally J, Mao H, et al: Inhibition of histone deacetylase activity attenuates renal fibroblast activation and interstitial fibrosis in obstructive nephropathy. Am J Physiol Renal Physiol. 297:F996–F1005. 2009. View Article : Google Scholar : PubMed/NCBI
21	Cregger M, Berger AJ and Rimm DL: Immunohistochemistry and quantitative analysis of protein expression. Arch Pathol Lab Med. 130:1026–1030. 2006.PubMed/NCBI
22	Hewitson TD, Ho WY and Samuel CS: Antifibrotic properties of relaxin: in vivo mechanism of action in experimental renal tubulointerstitial fibrosis. Endocrinol. 151:4938–4948. 2010. View Article : Google Scholar
23	Yang T, Vesey DA, Johnson DW, Wei MQ and Gobe GC: Apoptosis of tubulointerstitial chronic inflammatory cells in progressive renal fibrosis after cancer therapies. Transl Res. 150:40–50. 2007. View Article : Google Scholar : PubMed/NCBI
24	Izquierdo MC, Sanz AB, Mezzano S, et al: TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int. 81:1098–1107. 2012. View Article : Google Scholar : PubMed/NCBI
25	Figueroa-Romero C, Iniguez-Lluhi JA, Stadler J, et al: SUMOylation of the mitochondrial fission protein Drpl occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 23:3917–3927. 2009. View Article : Google Scholar : PubMed/NCBI
26	Brooks C, Cho SG, et al: Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis. Am J Physiol Cell Physiol. 300:C447–C455. 2011. View Article : Google Scholar : PubMed/NCBI
27	Wang H, Lim PJ, Karbowski M and Monteiro MJ: Effects of overexpression of huntingtin proteins on mitochondrial integrity. Hum Mol Genet. 18:737–752. 2009. View Article : Google Scholar : PubMed/NCBI
28	Brooks C, Cho SG, Wang CY, Yang T and Dong Z: Fragmented mitochondria are sensitized to Bax insertion and activation during apoptosis. Am J Physiol Cell Physiol. 300:C447–C455. 2011. View Article : Google Scholar : PubMed/NCBI
29	Ghezzi P and Brines M: Erythropoietin as an antiapoptotic, tissue-protective cytokine. Cell Death Differ. 11 (Suppl 1):S37–S44. 2004. View Article : Google Scholar : PubMed/NCBI
30	Ergur BU, Kiray M, Pekcetin C, et al: Protective effect of erythropoietin pretreatment in testicular ischemia-reperfusion injury in rats. J Pediatr Surg. 43:722–728. 2008. View Article : Google Scholar : PubMed/NCBI
31	Kitamura H, Isaka Y, Takabatake Y, et al: Nonethropoietic derivative of erythropoietin protect against tubulointerstitial injury in a unilateral ureteral obstruction model. Nephrol Dial Transplant. 23:1521–1528. 2008. View Article : Google Scholar : PubMed/NCBI
32	Kuriyams S, Tomonari H, Tokudome G, et al: Association of angiotensinogen gene polymorphism with erythropoietin-induced hypertension: a preliminary report. Hypertens Res. 24:501–505. 2001. View Article : Google Scholar : PubMed/NCBI
33	Jungers P, Choukroun G, Oualim Z, Robino C, Nguyen AT and Man NK: Beneficial influence of recombinant human erythropoietin therapy on the rate of progression of chronic renal failure in predialysis patients. Nephrol Dial Transplant. 16:307–312. 2001. View Article : Google Scholar : PubMed/NCBI
34	Nakazawa Y, Nishino T, Obata K, et al: Recombinant human erythropoietin attenuates renal tubulointerstitial injury in murine adriamycin-induced nephropathy. J Nephrol. 26:527–533. 2013. View Article : Google Scholar : PubMed/NCBI