Tanshinone IIA mitigates peritoneal fibrosis by inhibiting EMT via regulation of TGF-β/smad pathway

Purpose: To explore the effects of tanshinone IIA (T-IIA) on Dianeal-N PD-4 (PDF)-induced expression of fibrogenic cytokines in human peritoneal mesothelial cells (HPMCs), and to elucidate the mechanisms of action involved. Methods: Seven groups of HPMCs were used in the study: control group, PDF group, T-IIA group, LY364947 group, and 2 transforming growth factor-β (TGF-β) groups (TGF-β+ 50 μM T-IIA and TGF-β+ 100 μM T- IIA). The expression levels of mRNA and protein of TGF-β, smad2, smad7, α-smooth muscle actin(α-SMA), fibronectin, collagen І, E-cadherin, N-cadherin, matrix metalloprotein-2(MMP-2), and MMP-9 in the various groups were determined by reverse transcription-polymerase chain reaction (RTPCR) and Western blotting as appropriate. Results: The expressions of α-SMA, fibronectin, collagen І, TGF-β and smad2 were significantly upregulated in HPMCs by PDF treatment, but smad7 was down-regulated, relative to the control group (p < 0.01).These PDF-induced effects were reversed by T-IIA (p < 0.05). Inhibition of TGF-β/smad pathway by LY364947 treatment led to significant decrease in the expressions of fibrosis-related proteins, when compared with PDF group (p < 0.05). TGF-β treatment also produced numerous spindleshaped HPMCs characteristic of epithelial-mesenchymal transition (EMT). However, this morphological transition was alleviated, and the expression levels of EMT-related proteins were significantly downregulated by exposure to the two doses of T-IIA (p < 0.05). Conclusion: Tanshinone IIA inhibits EMT in HPMCs by regulating TGF-β/smad pathway, thus mitigating peritoneal fibrosis. Therefore, T-IIA has promising potential as a new drug for the treatment of peritoneal dialysis (PD)-induced fibrosis. Keywords: Peritoneal dialysis, Peritoneal fibrosis, Tanshinone IIA, Epithelial-mesenchymal transitio

Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment

Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFβ1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI

Effectiveness and Safety of Peritoneal Dialysis Treatment in Patients with Refractory Congestive Heart Failure due to Chronic Cardiorenal Syndrome

Aims. To evaluate the effectiveness and safety of peritoneal dialysis (PD) in treating refractory congestive heart failure (RCHF) with cardiorenal syndrome (CRS). Methods. A total of 36 patients with RCHF were divided into type 2 CRS group (group A) and non-type 2 CRS group (group B) according to the patients’ clinical presentations and the ratio of serum urea to creatinine and urinary analyses in this prospective study. All patients were followed up till death or discontinuation of PD. Data were collected for analysis, including patient survival time on PD, technique failure, changes of heart function, and complications associated with PD treatment and hospitalization. Results. There were 27 deaths and 9 patients quitting PD program after a follow-up for 73 months with an average PD time of 22.8±18.2 months. A significant longer PD time was found in group B as compared with that in group A (29.0±19.4 versus 13.1±10.6 months, p=0.003). Kaplan–Meier curves showed a higher survival probability in group B than that in group A (p<0.001). Multivariate regression demonstrated that type 2 CRS was an independent risk factor for short survival time on PD. The benefit of PD on the improvement of survival and LVEF was limited to group B patients, but absent from group A patients. The impairment of exercise tolerance indicated by NYHA classification was markedly improved by PD for both groups. The technique survival was high, and the hospital readmission was evidently decreased for both group A and group B patients. Conclusions. Our data suggest that PD is a safe and feasible palliative treatment for RCHF with type 2 CRS, though the long-term survival could not be expected for patients with the type 2 CRS. Registration ID Number is ChiCTR1800015910