Department of Nephrology, Dongying People's Hospital, Dongying, Shandong, P. R. China.
Department of Nephrology, Dongying People's Hospital, Dongying, Shandong, P. R. China.
Arch Med Res. 2018 Apr;49(3):164-171. doi: 10.1016/j.arcmed.2018.08.002. Epub 2018 Aug 14.
To investigate how miR-302b affect the calcium-phosphorus metabolism and vascular calcification (VC) of rats with chronic renal failure (CRF) via the regulation of bone morphogentic proteins 2/Runt-related transcription factor 3/Osterix (BMP-2/Runx2/Osterix) signaling pathway.
SD rats were selected to establish CRF rat models and assigned into Sham, CRF, CRF + miR-302b, and CRF + miR-NC groups. The biochemical indexes of rats were detected at 8th and 12th week. Besides, HE staining and Von Kossa staining were performed to monitor renal structural changes and VC respectively; and quantitative real-time PCR (qRT-PCR) and Western blotting to evaluate the expressions of miR-302b and BMP-2/Runx2/Osterix signaling pathway separately.
HE and Von Kossa staining showed evident vascular calcification in rats from CRF and CRF + miR-NC groups with a large number of black granules deposited in renal artery compared with Sham group, but was improved in rats in the CRF + miR-302b group compared to those in the CRF group. Besides, rats in the CRF group had elevated levels of Scr, BUN, P, Cys C, and PTH, as well as the mRNA and protein expression of BMP-2, Runx2, and Osterix, and reduced serum Ca and miR-302b levels in a time-dependent manner (all p <0.05), which was in a completely opposite tendency in the CRF + miR-302b group (all p <0.05).
miR-302b may improve calcium-phosphorus metabolism, and inhibit VC to alleviate the condition of CRF rats possibly associated with the BMP-2/Runx2/Osterix pathway, opening a new idea for CRF therapy.
探讨 miR-302b 通过调控骨形态发生蛋白 2/ runt 相关转录因子 3/成骨特异性转录因子 2（BMP-2/Runx2/Osterix）信号通路对慢性肾衰竭（CRF）大鼠钙磷代谢和血管钙化（VC）的影响。
选取 SD 大鼠建立 CRF 大鼠模型，分为假手术组、CRF 组、CRF+miR-302b 组和 CRF+miR-NC 组。在第 8 周和第 12 周检测大鼠的生化指标。此外，通过 HE 染色和 Von Kossa 染色分别监测肾脏结构变化和 VC；通过定量实时 PCR（qRT-PCR）和 Western blot 分别评估 miR-302b 和 BMP-2/Runx2/Osterix 信号通路的表达。
HE 和 Von Kossa 染色显示，与假手术组相比，CRF 组和 CRF+miR-NC 组大鼠的肾动脉有明显的血管钙化，有大量黑色颗粒沉积，而 CRF+miR-302b 组大鼠的血管钙化程度较 CRF 组大鼠有所改善。此外，CRF 组大鼠血清肌酐（Scr）、尿素氮（BUN）、磷（P）、半胱氨酸蛋白酶抑制剂 C（Cys C）、甲状旁腺激素（PTH）水平以及 BMP-2、Runx2、Osterix mRNA 和蛋白表达水平均呈时间依赖性升高（均 P<0.05），而 CRF+miR-302b 组大鼠血清钙和 miR-302b 水平呈时间依赖性降低（均 P<0.05）。
miR-302b 可能通过 BMP-2/Runx2/Osterix 通路改善钙磷代谢，抑制 VC，从而缓解 CRF 大鼠的病情，为 CRF 治疗提供了新的思路。
