Exploring the promotional effect of umbilical cord mesenchymal stem cells on wound healing in a diabetes model based on autophagy pathway
Objective To explore the promotional effects and potential mechanisms of umbilical cord mesenchymal stem cells(hUC-MSCs)in promoting wound healing in diabetic rats from the perspective of autophagy pathway HIF-1α/BNIP3/Beclin-1.Methods The rats were randomly divided into blank group,model group,MSC group,MSCHIF-1α group,and autophagy inhibitor group(CQ group)using the random number table method.Type 2 diabetes model was induced by high-fat feeding combined with intra-peritoneal injection of low-dose streptozotocin.Total dermal excision trauma was done on the back of rats to construct a skin wound in-jury model.The wound healing rate was calculated after the trauma.Hematoxylin staining was used to observe the tissue structure of the wound skin,and Masson staining was used to observe the colla-gen fibre deposition in the wound skin tissue.Immunohistochemical staining was used to observe the capillary neovascularisation of the trauma.Transmission electron microscopy was used to observe the au-tophagy status and ultrastructure of the tissue cells in the trauma.Western blotting was used to analyze the expression levels of HIF-1α,BNIP3,Beclin-1 and LC3 proteins in the traumatic tissues.Results Compared with the blank group,the wound healing rate,the propor-tion of CD31 positively stained cells in the wound tissue,as well as the protein expression of HIF-1α,BNIP3,Beclin-1,and the level of LC3II/LC3I in the model group were significantly reduced(P<0.05),while the time to complete wound healing and the thickness of the scar were significantly increased(P<0.05).Compared with the model group,the wound healing rate,the proportion of CD31-posi-tively stained cells in the wound tissue,and the protein expression of HIF-1α,BNIP3,Beclin-1,and the level of LC3II/LC3I in the MSC group were significantly increased(P<0.05),whereas the time for complete healing of the wound and the thickness of the scar were significantly increased and decreased(P<0.05);Compared with the MSC group,the wound healing rate,the proportion of CD31-positively stained cells,and the protein expression of HIF-1α,BNIP3,and Beclin-1,as well as the level of LC3II/LC3I in the MSCHIF-1α group were significantly increased(P<0.05),whereas the time to complete wound healing and scar thickness were signifi-cantly decreased(P<0.05).Compared with the MSCHIF-1α group,the wound healing rate,the proportion of CD31-positively stained cells in the wound tissue,as well as the protein expression of HIF-1α,BNIP3,Beclin-1,and the level of LC3II/LC3I in the CQ group were significantly decreased(P<0.05),whereas the time to complete healing of the wound and the thickness of the scar were signifi-cantly increased(P<0.05).Conclusion hUC-MSCs were able to improve traumatic tissue injury,promote granulation tissue growth and angiogenesis,and accelerate wound healing in diabetic rats,and the mechanism may be achieved by regulating the activa-tion of autophagy mediated by the HIF-1α/BNIP3/Beclin-1 signaling pathway.
human umbilical cord mesenchymal stem cellsdiabeteswound healingHIF-1α/BNIP3/Beclin-1 signaling pathwayautophagy
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