image: A-F, The IGFBP7 knockdown promote DPSCs senescence and attenuated tissue regeneration in vivo. G-H, The IGFBP7 knockdown inhibits the metabolism of DPSCs. I-J, The IGFBP7 overexpression promotes the metabolism of DPSCs. K-N, The IGFBP7 inhibits transcription of p21 by decreasing H3K36ac. O, Schematic diagram of the mechanism. view more
Credit: ©Science China Press
Cellular senescence leads to dysfunction of stem cells, which in turn severely impairs tissue homeostasis and tissue regeneration. How to effectively regulate the senescence of mesenchymal stem cells (MSCs) is crucial to maintain tissue function and improve the efficiency of tissue regeneration.
The insulin-like growth factor (IGF)-insulin-like growth factor binding protein (IGFBP) system is closely associated with the maintenance and differentiation of MSCs. It is involved in age-related diseases or senescence processes in a wide range of organisms from nematodes to mammals. But its detailed function and underlying mechanisms in stem cell senescence and tissue regeneration need further investigation.
Here, the research group of Academician Songlin Wang has discovered that IGFBP7 can prevent senescence and enhance osteogenic differentiation potential of dental pulp-derived mesenchymal stem cells (DPSCs).
By gain-of-function or loss-of-function of IGFBP7, the team found that IGFBP7 enhanced the mitochondrial oxidative phosphorylation and glycolysis capacity of DPSCs, and promoted the expression of mitochondrial biogenesis-related genes and key enzymes of glycolysis in DPSCs. Further, IGFBP7 was found to significantly upregulate the expression level of SIRT1, which induced deacetylation of H3K36ac and caused a reduction of the binding affinity of H3K36ac to p21 promoter, resulting in decrease of p21 transcription. Subsequently, researchers used ROT or coenzyme Q10 to block or activate the mitochondrial electron transport chain (ETC) in DPSCs, confirming the role of IGFBP7 in preventing senescence and promoting tissue regeneration in DPSCs through metabolic activities (see below).
These new exciting results add to growing evidence that the role of IGFBP7 in the cellular senescence process and lay the foundation for the development of new therapeutic strategies to promote tissue regeneration.
See the article:
Insulin-like growth factor binding proteins 7 prevents dental pulp-derived mesenchymal stem cell senescence via metabolic downregulation of p21
https://doi.org/10.1007/s11427-021-2096-0
Journal
Science China Life Sciences