Long noncoding RNA‑p21 modulates cellular senescence via the Wnt/β‑catenin signaling pathway in mesenchymal stem cells

Xia,Wenzheng; Zhuang,Lei; Deng,Xia; Hou,Meng

doi:10.3892/mmr.2017.7430

Long noncoding RNA‑p21 modulates cellular senescence via the Wnt/β‑catenin signaling pathway in mesenchymal stem cells

Authors:
- Wenzheng Xia
- Lei Zhuang
- Xia Deng
- Meng Hou
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Affiliations: Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Hepatobiliary Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Radiation Oncology, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: September 7, 2017 https://doi.org/10.3892/mmr.2017.7430
Pages: 7039-7047

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Abstract

Mesenchymal stem cell (MSC)‑based therapies have demonstrated efficacy in animal models of cardiovascular diseases. However, MSCs decrease in quantity and quality with age, which reduces their capacity for damage repair. Long noncoding (lnc) RNAs regulate gene transcription and the fate of post‑transcriptional mRNA, affecting a broad range of age‑associated physiological and pathological conditions, including cardiovascular disease and cancer cell senescence. However, the functional role of lncRNAs in stem cell senescence remains largely unknown. The present study isolated bone marrow‑derived MSCs from young (8‑week‑old) and aged (18‑month‑old) male C57BL/6 mice. Cell proliferation was measured using a Cell Counting kit‑8 assay, and the secretion of vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and insulin‑like growth factor was measured by ELISA. Western blotting was performed to investigate β‑catenin protein expression. Oxidative stress was evaluated by detecting reactive oxygen species, and the activity of superoxide dismutase and malondialdehyde. MSCs isolated from aged mice demonstrated reduced proliferation and paracrine signaling, and increased oxidative stress and expression of lincRNA‑p21compared with MSCs from younger mice. Silencing lincRNA‑p21 in aged MSCs using small interfering RNA (siRNA) enhanced cell growth and paracrine function, and decreased oxidative stress. These results were reversed when β‑catenin expression was silenced using siRNA. In conclusion, lincRNA‑p21 may serve a role in MSC senescence, and silencing lincRNA‑p21 may rejuvenate MSCs by interacting with the Wnt/β‑catenin signaling pathway. Targeting lincRNA‑p21 may therefore have important therapeutic implications for restoring endogenous MSCs in aged individuals.

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