Intermedin1‑47 inhibits high phosphate‑induced vascular smooth muscle cell calcification by regulating Wnt/β‑catenin signaling

Zhang,Yin; Tang,Naiwang; Zhou,Jinjie

doi:10.3892/mmr.2021.12373

Intermedin1‑47 inhibits high phosphate‑induced vascular smooth muscle cell calcification by regulating Wnt/β‑catenin signaling

Authors:
- Yin Zhang
- Naiwang Tang
- Jinjie Zhou
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Affiliations: Department of Geriatrics, Shanghai Fourth Rehabilitation Hospital, Shanghai 200042, P.R. China, Department of Respiratory, Central Hospital of Xuhui District, Shanghai 200031, P.R. China, Department of Cardiology, Central Hospital of Huangpu District, Shanghai 200002, P.R. China
Published online on: August 16, 2021 https://doi.org/10.3892/mmr.2021.12373
Article Number: 733

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Abstract

Vascular calcification is a major risk factor for cardiovascular disease and accounts for a large proportion of deaths from cardiovascular disease in patients with chronic kidney disease. The high incidence, rapid progression and irreversibility of vascular smooth muscle cell (VSMC) calcification in patients has attracted attention. In the present study, the effect of intermedin1‑47 (IMD1‑47), an important isoform of intermedin, was investigated on the calcification of rat cardiovascular VSMCs induced by high phosphate (HP). To stimulate osteoblast‑like differentiation and calcification in rat VSMCs, 10 mM β‑sodium glycerophosphate was used. The VSMCs were then treated with three doses of IMD1‑47 and the effects of IMD1‑47 on VSMC calcification, on the expression of osteogenic markers [osteoprotegerin, Runt‑related transcription factor 2 (Runx2) and osteopontin (OPN)] and on alkaline phosphatase (ALP) activity were assessed. HP treatment significantly enhanced the cellular calcium content of VSMCs, the expression of osteogenic markers, and ALP activity, while IMD1‑47 significantly reversed these effects in a dose‑dependent manner. The protein expression levels of Wnt1, Wnt3a and active β‑catenin were determined and it was found that IMD1‑47 significantly inhibited their expression. Following β‑catenin silencing, the protein expression levels Runx2 and OPN were increased compared with the IMD1‑47 treatment alone, indicating a role for the Wnt/β‑catenin pathway in the effects of IMD1‑47 on osteogenic markers. The present study suggested that IMD1‑47 inhibited HP‑induced VSMC calcification by regulating the Wnt/β‑catenin signaling pathway.

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