It has been demonstrated that ERK1/2 pathway plays a vital role in EMT. An ancient formula named QiFu Decoction (QFD) has been used to treat CON in China for many years. Nevertheless, the underlying mechanisms in vivo remain unknown. In this research, we investigated the effects of the combination of astragaloside and aconitine, two effective ingredients extracted from QFD in CON rats, and the related-mechanism of ameliorating RTIF by modulating ERK1/2 pathway. Methods: Sprague-Dawley
(SD) rats were given adenine (150 mg/kg/d) for 2 weeks and unilateral ureteral obstruction (UUO) operation at the end of week 2 to produce CON. Some BAY 73-4506 CON rats were given the combination of astragaloside and aconitine (0.4 g/kg/d), while some others were given enalapril
(0.02 g/kg/d) for 3 weeks. Age and weight-matched rats were used as normal controls. Renal function, urinary beta2-MG and NAG, as well as tubulointerstitial histopathological changes were detected, respectively. The protein expressions of phenotype of EMT in renal tissue including E-cadherin and alpha-SMA, profibrotic cytokines containing TGF-beta1 and CTGF, as well as phosphorylated-ERK1/2 (p-ERK1/2), the key molecule in ERK 1/2 pathway, were observed by Western blots, respectively. Results: Adenine and UUO operation learn more successfully induced CON models, which performed significant abnormal renal function, mass low-molecular Calpain weight proteinuria, and extracellular matrix deposition in tubulointerstitial district. After orally given the combination therapy for 3 weeks, low-molecular weight proteinuria and renal tubulointerstitial fibrosis were reduced. In addition, the E-cadherin protein
expression was up-regulated, while alpha-SMA, TGF-beta1, CTGF, and p-ERK1/2 protein expressions were down-regulated. However, the renal dysfunction cannot be improved by the combination therapy. Abnormalities in urinary parameters and renal tubulointerstitial fibrosis could also be attenuated by enalapril. Conclusion: RTIF can be ameliorated in CON rats by the combination of astragaloside and aconitine treatment via regulating E-cadherin, alpha-SMA, TGF-beta1, and CTGF protein expressions, as well as inhibiting ERK1/2 pathway. HAGIWARA MASAHIRO, HIWATASHI AKIRA, KAI HIRAYASU, USUI JOICHI, MORITO NAOKI, SAITO CHIE, YOH KEIGYO, YAMAGATA KUNIHIRO Department of Nephrology, Faculty of Medicine, University of Tsukuba Introduction: Podocalyxin (PCX), the major sialoprotein of glomerular epithelial cells (podocytes) is expressed on apical membrane, and helps maintain the architecture of the foot process and the patency of the filtration slits.