Background: It has been reported that loss of PCBP2 led to increased reactive oxygen species (ROS) production and accelerated cell aging. Knockdown of PCBP2 in HCT116 cells leads to significant down-regulation of fibroblast growth factor 2 (FGF2). Here, we tried to elucidate the intrinsic factors and potential mechanisms of BMSCs aging from the interactions among PCBP2, ROS and FGF2.

Methods: Unlabeled quantitative proteomics were performed to show differentially expressed proteins in the replicative senescent human-derived bone marrow stromal cells (RS-hBMSCs). ROS and FGF2 were detected in the loss-and-gain cell function experiments of PCBP2. The function recovery experiments were performed to verify whether PCBP2 regulates cell function through ROS/FGF2-dependent ways.

Results: PCBP2 expression was significantly lower in P10-hBMSCs. Knocking down the expression of PCBP2 inhibited the proliferation while accentuated the apoptosis and cell arrest of RS-hBMSCs. PCBP2 silence could increase the production of ROS. On the contrary, overexpression of PCBP2 increased the viability of both P3-hBMSCs and P10-hBMSCs significantly. Meanwhile, over-expression of PCBP2 led to significantly reduced expression of FGF2. Overexpression of FGF2 significantly offset the effect of PCBP2 overexpression in P10-hBMSCs, leading to decreased cell proliferation, increased apoptosis and reduced G0/G1 phase ratio of the cells.

Conclusion: This study initially elucidates that PCBP2 as an intrinsic aging factor regulates the replicative senescence of hBMSCs through the ROS-FGF2 signaling axis.

The authors have declared no competing interest.

This study was supported by the National Natural Science Foundation of China (82172474).

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Experimental protocols involving human specimens were approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHECNSFC2021159).

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