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Impact of miR-302b on Calcium-phosphorus Metabolism and Vascular Calcification of Rats with Chronic Renal Failure by Regulating BMP-2/Runx2/Osterix Signaling Pathway.

OBJECTIVE: 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.

METHODS: 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.

RESULTS: 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).

CONCLUSION: 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.

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