Published online Apr 26, 2021. doi: 10.4252/wjsc.v13.i4.317
Peer-review started: February 1, 2021
First decision: February 28, 2021
Revised: March 11, 2021
Accepted: March 29, 2021
Article in press: March 29, 2021
Published online: April 26, 2021
As human placenta-derived mesenchymal stem cells (hP-MSCs) exist in a physiologically hypoxic microenvironment, various studies have focused on the influence of hypoxia. However, the underlying mechanisms remain to be further explored.
The aim was to reveal the possible mechanisms by which hypoxia enhances the proliferation of hP-MSCs.
A hypoxic cell incubator (2.5% O2) was used to mimic a hypoxic micro
Hypoxia enhanced hP-MSC proliferation, increased the expression of cyclin E1, cyclin-dependent kinase 2, and cyclin A2, and decreased the expression of p21. Under hypoxia, CD99 expression was increased by HIF-1α. CD99-specific small interfering RNA or the ERK1/2 signaling inhibitor PD98059 abrogated the hypoxia-induced increase in cell proliferation.
Hypoxia promoted hP-MSCs proliferation in a manner dependent on CD99 regulation of the MAPK/ERK signaling pathway in vitro.
Core Tip: This study demonstrated the potential of hypoxic conditions to enhance the proliferation capacity of human placenta-derived mesenchymal stem cells (hP-MSCs). RNA sequencing assays and molecular biology experiments found that a novel CD99 gene was involved in hypoxia-mediated promotion of hP-MSC proliferation. Furthermore, CD99 activated pathways that transported ERK1/2 to the nucleus, increasing the activity of cell cycle-associated proteins. Hypoxia-inducible factor 1α-mediated CD99 played a role in proliferation by regulating the MAPK/ERK signaling pathway.