Erratum: Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction: Erratum.

[This corrects the article DOI: 10.7150/ijms.26954.].

Role of Sirolimus in renal tubular apoptosis in response to unilateral ureteral obstruction.

Renal tubule cell apoptosis plays a pivotal role in the progression of chronic renal diseases. The previous study indicates that Sirolimus is effective on unilateral ureteral obstruction (UUO)-induced renal fibrosis. However, the role of Sirolimus in renal tubular apoptosis induced by UUO has not yet been addressed. The aim of this study was to determine the role of Sirolimus in renal tubular apoptosis induced by UUO. Male Sprague-Dawley rats were divided into three groups, sham-operated rats, and after which unilateral ureteral obstruction (UUO) was performed: non-treated and sirolimus-treated (1mg/kg). After 4, 7 and 14 d, animals were sacrificed and blood, kidney tissue samples were collected for analyses. Histologic changes and interstitial collagen were determined microscopically following HE and Masson's trichrome staining. The expression of PCNA was investigated using immunohistochemistry and the expression of Bcl-2, Bax, caspase-9, and caspase-3 were investigated using Western blot in each group. Tubular apoptotic cell deaths were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Sirolimus administration resulted in a significant reduction in tubulointerstitial fibrosis scores. After UUO, there was an increase in tubular and interstitial apoptosis in untreated controls as compared to Sirolimus treatment rats (P<0.05). In addition, the expression of PCNA, Bcl-2, Bax, caspase-9, and caspase-3 in obstructed kidney was characterized by immunohistochemistry and Western blot analyses demonstrating that sirolimus treatment significantly reduced PCNA, Bax, caspase-9 and cleaved caspase-3 expression compared to those observed in controls (P<0.05), whereas, Bcl-2 in the obstructed kidney were decreased in untreated controls compared to Sirolimus treatment rats subjected to the same time course of obstruction (P<0.05). We demonstrated a marked renoprotective effect of sirolimus by inhibition of UUO-induced renal tubular apoptosis in vivo.

The role of sildenafil in the development of transplant arteriosclerosis in rat aortic grafts.

Chronic rejection (CR), which is characterized histologically by progressive graft arteriosclerosis, remains a significant barrier to the long-term survival of a graft. Sildenafil has been shown to protect vascular endothelial cells. In this study, we found that sildenafil significantly reduces the thickness of transplant vascular intima in a rat aortic transplant model. Moreover, sildenafil dramatically decreased the expression of transforming growth factor-ß1 (TGF-ß1), vascular endothelial growth factor (VEGF), and α-smooth muscle actin (α-SMA) in the grafted aortas and increased the concentrations of cyclic guanosine monophosphate (cGMP) and endothelial nitric oxide synthase (eNOS) in serum. Furthermore, the ratio of regulatory T (Treg) cells and the expression of FoxP3 were increased, and the ratio of Th17 cells was decreased in the sildenafil-treated group. These results demonstrate that sildenafil enhances nitric oxide (NO) signaling by increasing the availability of cGMP, leading to an increase in the ratio of Treg/Th17 cells to attenuate transplant arteriosclerosis in a rat aortic transplant model.