Research on the Mechanism of Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Delivering circ-Snhg11 to Promote Diabetic Wound Healing

Jingyu Qian; Longji Ye; Xiaoyun Tang; Panpan Jin; Junfeng  Shao

doi:10.54097/4dz6jj69

Authors

Jingyu Qian
Longji Ye
Xiaoyun Tang
Panpan Jin
Junfeng Shao

DOI:

https://doi.org/10.54097/4dz6jj69

Keywords:

circ-Snhg11, Exosomes, Diabetic Wound Healing, Ferroptosis, SLC7A11, miR-144-3p

Abstract

Background: The ability of BMSC-derived exosomes (BMSC-Exos) to accelerate diabetic wound healing has been observed, but the underlying mechanism has not been fully elucidated.Methods: Differential expression of circRNA in skin tissue before and after exosome treatment was analyzed using second-generation sequencing technology. The targeting relationship between circRNA and downstream targets was detected using a luciferase reporter gene assay. Results: Exosome treatment significantly promoted diabetic wound healing. NGS results indicated that circ-Snhg11 was involved in exosome-mediated tissue repair. Knockdown of circ-Snhg11 attenuated the effect of exosomes on accelerating diabetic wound healing. Luciferase reporter gene data confirmed the targeting interaction between circ-Snhg11, SLC7A11, and miR-144-3p. Conclusion: BMSC-Exos promote diabetic wound healing by delivering circ-Snhg11, which is related to the regulation of endothelial cell ferroptosis mediated by SLC7A11/GPX4.

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References

[1] Yang J, Chen Z, Pan D, Li H, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomes combined Pluronic F127 hydrogel promote chronic diabetic wound healing and complete skin regeneration. Int J Nanomedicine. 2020,15: 5911-26.

[2] Everett E, Mathioudakis N. Update on management of diabetic foot ulcers. Ann N Y Acad Sci. 2018,1411(1):153-65.

[3] Li S, Li Y, Wu Z, et al. Diabetic ferroptosis plays an important role in triggering inflammation in diabetic wound. Am J Physiol Endocrinol Metab. 2021,321(4):E509-20.

[4] Liu W, Yu M, Xie D, et al. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res Ther. 2020,11(1):259.

[5] Kasuya A, Tokura Y. Attempts to accelerate wound healing. J Dermatol Sci. 2014,76(3):169-72.

[6] Gentile P, Sterodimas A, Pizzicannella J, et al. Systematic review: allogenic use of stromal vascular fraction (SVF) and decellularized extracellular matrices (ECM) as advanced therapy medicinal products (ATMP) in tissue regeneration. Int J Mol Sci. 2020,21(14):4982.

[7] Gentile P, Garcovich S. Adipose-derived mesenchymal stem cells (AD-MSCs) against ultraviolet (UV) radiation effects and the skin photoaging. Biomedicines. 2021,9(5):532.

[8] Wang M, Wang C, Chen M, et al. Efficient angiogenesis-based diabetic wound healing/skin reconstruction through bioactive antibacterial adhesive ultraviolet shielding nanodressing with exosome release. ACS Nano. 2019,13(9):10279-93.

[9] Yu M, Liu W, Li J, et al. Exosomes derived from atorvastatin-pretreated MSC accelerate diabetic wound repair by enhancing angiogenesis via AKT/eNOS pathway. Stem Cell Res Ther. 2020,11(1):350.

[10] Li S, Li Y, Zhu K, He W, Guo X, Wang T, Gong S, Zhu Z. Exosomes from mesenchymal stem cells: Potential applications in wound healing. Life Sci. 2024,357:123066.

[11] Raghav PK, Mann Z. Nano-Delivery Revolution: Harnessing Mesenchymal Stem Cell-Derived Exosomes’ Potential for Wound Healing. Biomedicines. 2024;12(12):2791.

[12] Tkach M, Thery C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016,164 (6): 1226-32.

[13] Zhang L, Zeng M, Tang F, et al. Circ-PNPT1 contributes to gestational diabetes mellitus (GDM) by regulating the function of trophoblast cells through miR-889-3p/PAK1 axis. Diabetol Metab Syndr. 2021,13(1):58.

[14] Lu GD, Cheng P, Liu T, et al. BMSC-derived exosomal miR-29a promotes angiogenesis and osteogenesis. Front Cell Dev Biol. 2020,8:608521.

[15] Pomatto M, Gai C, Negro F, et al. Differential therapeutic effect of extracellular vesicles derived by bone marrow and adipose mesenchymal stem cells on wound healing of diabetic ulcers and correlation to their cargoes. Int J Mol Sci. 2021, 22 (8): 3851.

[16] Wang C, Wang M, Xu T, et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration. Theranostics. 2019,9(1):65-76.

[17] Cao G, Meng X, Han X, et al. Exosomes derived from circRNA Rtn4-modified BMSCs attenuate TNF-alpha-induced cytotoxicity and apoptosis in murine MC3T3-E1 cells by sponging miR-146a. Biosci Rep. 2020,40(5).

[18] Fu M, Fang L, Xiang X, et al. Microarray analysis of circRNAs sequencing profile in exosomes derived from bone marrow mesenchymal stem cells in postmenopausal osteoporosis patients. J Clin Lab Anal. 2022,36(1):e23916.

[19] Zhou J, Ding Y, Zhang Y, et al. Exosomes from bone marrow-derived mesenchymal stem cells facilitate corneal wound healing via regulating the p44/42 MAPK pathway. Graefes Arch Clin Exp Ophthalmol. 2023,261(3):723-34.

[20] Shen C, Tao C, Zhang A, et al. Exosomal microRNA-93-3p secreted by bone marrow mesenchymal stem cells downregulates apoptotic peptidase activating factor 1 to promote wound healing. Bioengineered. 2022,13(1):27-37.

[21] Hui Z, Wang S, Li J, et al. Compound Tongluo Decoction inhibits endoplasmic reticulum stress-induced ferroptosis and promoted angiogenesis by activating the Sonic hedgehog pathway in cerebral infarction. J Ethnopharmacol. 2022,283: 114634.

[22] Yan J, Feng G, Ma L, et al. Metformin alleviates osteoarthritis in mice by inhibiting chondrocyte ferroptosis and improving subchondral osteosclerosis and angiogenesis. J Orthop Surg Res. 2022,17(1):333.