The HIFIA/LINC02913/IGF1R axis promotes the cell function of adipose-derived mesenchymal stem cells under hypoxia via activating the PI3K/AKT pathway

Abstract

Objective Promoting angiogenesis is crucial for tissue repair. Adipose-derived mesenchymal stem cells (ADSCs) are endowed with the ability of paracrine secretion of various angiogenic cytokines and the differentiation potential into endothelium-like cells to directly participate in angiogenesis. ADSCs are key seed cells for promoting angiogenesis in regenerative medicine and tissue engineering. This study aimed to explore the role and mechanism of C9orf106 (LINC02913) in the angiogenesis of ADSCs. Methods The microarray dataset GSE12884 was analyzed to identify the differentially expressed lncRNAs in ADSCs under normoxia and hypoxia. The expression of the key genes was detected using qRT-PCR, western blot assay (western blot), and immunofluorescence (IF) staining. The adipogenic ability and tube formation ability of ADSCs was detected using oil red O staining and tube formation assay, respectively. The regulatory relationship between hypoxia-inducible factor-1alpha (HIF1A) and LINC02913 was verified using chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay. A skin wound healing nude mice model was established. Hematoxylin and eosin (H&E) staining was applied to detect pathological skin damage. Immunohistochemistry (IHC) staining was used to determine the level of CD31 in skin tissues. Results LINC02913 expression was decreased in ADSCs under hypoxia; LINC02913 overexpression inhibited the proliferation, adipogenic ability, endothelial differentiation ability, and tube formation ability of ADSCs. ChIP assay and dual-luciferase reporter gene assay results showed that HIF1A could directly bind to the LINC02913 promoter region to inhibit its transcription. Through RNAact prediction and analysis of the correlation with LINC02913 expression, it was found that IGF1R may directly interact with LINCO02913. The HIF1A/LINC02913/IGF1R axis could activate the PI3K/AKT pathway to promote the biological function of ADSCs. Hypoxia-ADSCs significantly promoted vascularization in the wounded skin. The regulatory effect of LINC02913/IGF1R axis on hypoxia-ADSCs treated skin wound healing were verified. Conclusion The HIF1A/LINC02913/IGF1R axis promoted the proliferation, adipogenic ability, and tube formation ability of ADSCs under hypoxia via activating the PI3K/AKT pathway.

LOC646762 Is Involved in Adipogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells

“…In this study, adipogenic and osteogenic differentiation abilities of BMSCs were verified by performing Oil Red O and Alizarin Red S staining. 19 During adipogenic induction, the formation of lipid droplets was noted, whereas during osteogenic induction, the cells showed pleomorphism and calcium nodule formation. These results indicate that BMSCs have significant potential for adipogenic and osteogenic differentiation under various induction conditions, confirming their multidirectional differentiation properties.…”

“…In this study, adipogenic and osteogenic differentiation abilities of BMSCs were verified by performing Oil Red O and Alizarin Red S staining . During adipogenic induction, the formation of lipid droplets was noted, whereas during osteogenic induction, the cells showed pleomorphism and calcium nodule formation.…”

Investigating the Impact of Astragalus Polysaccharide on Angiogenesis in Human Adipose-Derived Stem Cells

“…In order to heal wounds and repair tissues, new capillaries must be formed. In addition to increasing blood flow to the wound, neovascularization provides adequate oxygen and nutrition to aid wound healing, removes local metabolites, and accelerates tissue repair [14] . After healing, angiogenesis occurs in the wound, including endothelial cell proliferation, migration and tube formation.…”