Jun Peng1, Chao Qin2, Shu-Yan Tian1, Jia-Qing Peng3. 1. Department of Nephrology, Jingzhou Central Hospital, Jingzhou, 434020, Hubei, China. 2. Department of Orthopaedics, Jingzhou Central Hospital, Jingzhou, Hubei, China. 3. Department of Nephrology, Jingzhou Central Hospital, Jingzhou, 434020, Hubei, China. peng_pjq30@sina.com.
Abstract
OBJECTIVE: To explore the effect of miR-93-mediated Wnt/β-catenin pathway on the vascular calcification (VC) of chronic renal failure (CRF). METHODS: SD rats were utilized to construct CRF models and divided into Control, CRF, CRF + LV (lentiviral vector)-miR-93 and CRF + LV-Con groups. Renal tissues collected from rats were performed hematoxylin and eosin (HE) staining and Masson staining, while the abdominal aorta was dissected for alizarin red staining and Von Kossa staining. VC-related genes were determined by qRT-PCR while Wnt/β-catenin pathway-related proteins were examined by Western blotting. RESULTS: As compared to Control group, the serum levels of blood urea nitrogen (BUN), serum creatinine (Scr), phosphorus (P), cystatin C (Cys-C) and 24-h urea protein (24 h Upro), and the scores of renal interstitial lesion and fibrotic area in rats from CRF group were elevated, with the increased calcified area of aorta as well as the enhanced calcium content and ALP. Meanwhile, rats in the CRF group had up-regulated expression of OPN, OCN, RUNX2 and BMP-2 and down-regulated expression of miR-93. As for the expression of Wnt/β-catenin pathway, rats in the CRF group had sharp increases in the protein expression of TCF4 and β-catenin, while α-SMA was down-regulated. However, changes of the above were reversed in rats from CRF + LV-miR-93 group, and TCF4 was confirmed to be a target gene of miR-93. CONCLUSION: MiR-93, via inhibiting the activity of Wnt/β-catenin pathway by targeting TCF4, can improve the renal function of CRF rats, thereby mitigating the vascular calcification of CRF.
OBJECTIVE: To explore the effect of miR-93-mediated Wnt/β-catenin pathway on the vascular calcification (VC) of chronic renal failure (CRF). METHODS: SD rats were utilized to construct CRF models and divided into Control, CRF, CRF + LV (lentiviral vector)-miR-93 and CRF + LV-Con groups. Renal tissues collected from rats were performed hematoxylin and eosin (HE) staining and Masson staining, while the abdominal aorta was dissected for alizarin red staining and Von Kossa staining. VC-related genes were determined by qRT-PCR while Wnt/β-catenin pathway-related proteins were examined by Western blotting. RESULTS: As compared to Control group, the serum levels of blood urea nitrogen (BUN), serum creatinine (Scr), phosphorus (P), cystatin C (Cys-C) and 24-h urea protein (24 h Upro), and the scores of renal interstitial lesion and fibrotic area in rats from CRF group were elevated, with the increased calcified area of aorta as well as the enhanced calcium content and ALP. Meanwhile, rats in the CRF group had up-regulated expression of OPN, OCN, RUNX2 and BMP-2 and down-regulated expression of miR-93. As for the expression of Wnt/β-catenin pathway, rats in the CRF group had sharp increases in the protein expression of TCF4 and β-catenin, while α-SMA was down-regulated. However, changes of the above were reversed in rats from CRF + LV-miR-93 group, and TCF4 was confirmed to be a target gene of miR-93. CONCLUSION: MiR-93, via inhibiting the activity of Wnt/β-catenin pathway by targeting TCF4, can improve the renal function of CRF rats, thereby mitigating the vascular calcification of CRF.
Authors: Efstathia K Kapsogeorgou; Vasiliki C Gourzi; Menelaos N Manoussakis; Haralampos M Moutsopoulos; Athanasios G Tzioufas Journal: J Autoimmun Date: 2011-05-31 Impact factor: 7.094
Authors: Antonio Bellasi; Laura Kooienga; Geoffrey A Block; Emir Veledar; David M Spiegel; Paolo Raggi Journal: J Nephrol Date: 2009 Mar-Apr Impact factor: 3.902
Authors: Odongua Sangidorj; Seung Hee Yang; Hye Ryoun Jang; Jung Pyo Lee; Ran-hui Cha; Sun Moon Kim; Chun Soo Lim; Yon Su Kim Journal: Am J Physiol Renal Physiol Date: 2010-05-19
Authors: Campbell R Sheen; Pia Kuss; Sonoko Narisawa; Manisha C Yadav; Jessica Nigro; Wei Wang; T Nicole Chhea; Eduard A Sergienko; Kapil Kapoor; Michael R Jackson; Marc F Hoylaerts; Anthony B Pinkerton; W Charles O'Neill; José Luis Millán Journal: J Bone Miner Res Date: 2015-05 Impact factor: 6.741