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

Abstract

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.

Mitochondrial dysfunction and endoplasmic reticulum stress in the promotion of fibrosis in obstructive nephropathy induced by unilateral ureteral obstruction

“…The current information strongly suggests that bioenergetics impairment triggers several alterations in mitochondrial homeostasis, among which we find: reduction in mitochondrial number and mass and in biogenesis, 33,58 shift of the dynamics towards fission, 90–94 disturbance in mitophagy flux 93,101 and the dysregulation in Ca +2 levels 67,69,70 . Given the close relationship between the ER and mitochondria, in UUO mitochondrial alterations also favor ER impairment, which can be explained by oxidative stress increase, 18,21,39 Ca +2 depletion, 61,67,69,70 and FA accumulation, 33,51 favoring ER stress‐increased cell damage 136,139 .…”

“…Additionally, in the renal tubulointerstitium, where Drp1 is normally expressed at low levels, UUO-OKs also show a temporal increase in the expression of Drp1. 94 In the same way, sirtuin 3 (SIRT3) is a deacetylase protein mainly localized in mitochondria, involved in the regulation of mitochondrial biogenesis and dynamics. 95,96 SIRT3 protein levels are decreased in UUO-OKs.…”

PPAR γ/TLR4/TGF-β1 axis mediates the protection effect of erythropoietin on cyclosporin A-induced chronic nephropathy in rat

“…The renal protective effect of EPO has been reported in many literatures. Zhao et al [16] found that EPO can improve renal dysfunction and interstitial fibrosis in rats with unilateral ureteral obstruction. Acikgoz' study showed that the antifibrotic effect of EPO on rats with obstructive renal fibrosis may be regulated by nuclear factor kappa B (NF-rB) signaling pathway [17].…”

Mitochondrial Dysfunction in Kidney Disease and Uremic Sarcopenia

“…Renoprotection is promoted via an anti-apoptotic effect from the expression of the EPO receptor, the reduction of the Bax/Bcl-XL ratio, the inhibition of cytochrome-c release into the cytosol, and the decrease of active caspase-3 expression. EPO treatment also reduces renal fibrosis in UUO model rats, and downregulates Drp1 overexpression to reduce mitochondria fission ( Zhao et al, 2015 ).…”