miR-31-5p Is a LIPUS-Mechanosensitive MicroRNA that Targets HIF-1α Signaling and Cytoskeletal Proteins

International Journal of Molecular Sciences

卷:20

Riccardo Alessandro¹  Alice Conigliaro¹  Stefania Setti²  Valeria Carina³  Lavinia Raimondi³  Viviana Costa³  Daniele Bellavia³  Angela De Luca³  Francesca Salamanna⁴  Milena Fini⁴  Gianluca Giavaresi⁴ 

[1] Department of BioMedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), University of Palermo, 90100 Palermo, Italy;

[2] IGEA SpA, 41012 Carpi (Modena), Italy;

[3] IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy;

[4] IRCCS Istituto Ortopedico Rizzoli, Laboratory of Preclinical and Surgical Studies, 40136 Bologna, Italy;

关键词: hypoxia;    mesenchymal stem cells;    microRNAs;    Rho family protein;    regenerative medicine;   

DOI  :  10.3390/ijms20071569

来源: DOAJ

【 摘 要 】

The roles of low-intensity pulsed ultrasound (LIPUS) and microRNAs (miRNAs) on hMSCs commitments have already been investigated; however, the effects of the application of their co-treatments in an in vitro cell model are still unknown. Our previous studies demonstrated that (i) LIPUS modulated hMSCs cytoskeletal organization and (ii) miRNA-675-5p have a role in HIF-1α signaling modulation during hMSCs osteoblast commitment. We investigated for the first time the role of LIPUS as promoter tool for miRNA expression. Thanks to bioinformatic analysis, we identified miR-31-5p as a LIPUS-induced miRNA and investigated its role through in vitro studies of gain and loss of function. Results highlighted that LIPUS stimulation induced a hypoxia adaptive cell response, which determines a reorganization of cell membrane and cytoskeleton proteins. MiR-31-5p gain and loss of function studies, demonstrated as miR-31-5p overexpression, were able to induce hypoxic and cytoskeletal responses. Moreover, the co-treatments LIPUS and miR-31-5p inhibitor abolished the hypoxic responses including angiogenesis and the expression of Rho family proteins. MiR-31-5p was identified as a LIPUS-mechanosensitive miRNAs and may be considered a new therapeutic option to promote or abolish hypoxic response and cytoskeletal organization on hMSCs during the bone regeneration process.

【 授权许可】

Unknown