MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

Abstract

Background/Aims: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

Estrogen Promotes cAMP Production in Mesenchymal Stem Cells by Regulating ADCY2

“…However, the serum levels of E2 were found to be significantly lower in women with preeclampsia (PE) than among controls (8,9). In accordance with this, the MSCs of the maternal fetal interface in PE patients, whether they come from the decidua or the umbilical cord, show slow growth, senescence, and impaired immunosuppression (10,11). After treatment with normal MSCs, the PE symptoms of PE-like mice were alleviated significantly (12).…”

Senile Osteoporosis: The Involvement of Differentiation and Senescence of Bone Marrow Stromal Cells

“…In addition, miR-34a has been identified to downregulate the expression of class-III histone deacetylase silent information regulator 1 (SIRT1), thus, resulting in the increased level of p21 levels, triggering senescence [127]. MiR-195 and miR-495 have also played roles in causing senescence in BMSCs [128,129].…”

miR‐155‐5p inhibition rejuvenates aged mesenchymal stem cells and enhances cardioprotection following infarction

“…Recently, increasing evidence has demonstrated that miRNAs play crucial roles in regulating the cellular senescence of MSCs (Meng et al, 2018; Yoo, Kim, Jung, Lee, & Kim, 2014). miR‐495 targets Bmi‐1 and induces MSC senescence, as evidenced by enhanced β‐galactosidase activity and reduced cell proliferation (Li et al, 2017). Moreover, miR‐29c‐3p is upregulated during the replicative senescence of MSCs and suppresses their functions by targeting CNOT6 to activate the p53‐p21 and p16‐pRB pathways (Shang et al, 2016).…”