Research Progress on the Promotion of Human Umbilical Vein Endothelial Cell (HUVECs) angiogenesis by Rhodiola Rosea and Exosomes through SDF-1/CXCR4 under High Glucose Environment
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i3.4442
Abstract
Angiogenesis disorder induced by a high glucose environment is a core pathological link in diabetic vascular complications such as diabetic foot ulcers and diabetic nephropathy, and the key mechanism is the persistent damage to vascular endothelial cell function caused by high glucose. Rhodiola rosea, a traditional highland Chinese medicinal herb, has anti-inflammatory, antioxidant and vasoprotective effects from its active ingredients (salidroside, tyrosol, etc.); Exosomes, which act as "nanocarriers" for intercellular communication, regulate angiogenesis by delivering bioactive substances. This article systematically reviews the research progress on the promotion of angiogenesis in human umbilical vein endothelial cells (HUVECs) by both through the SDF-1/CXCR4 signaling pathway in a high glucose environment: Both can upregulate SDF-1 expression, activate CXCR4 receptor, further activate downstream pathways such as PI3K/AKT and MAPK, and improve high glucose-induced oxidative stress and inflammatory microenvironment; Salidroside can relieve SDF-1 inhibition by regulating miR-210, and exosomes can directly carry SDF-1 or indirectly activate the pathway by targeting PTEN through miR-132. The current research has problems such as unclear molecular mechanisms, insufficient in vivo experiments, and lack of clinical translation. In-depth analysis of the regulatory relationship between the two and the SDF-1/CXCR4 pathway can provide new strategies for the treatment of diabetic vascular complications.
Keywords
Rhodiola rosea; Salidroside; Exosomes; High glucose environment; SDF-1/CXCR4 signaling pathway; Human umbilical vein endothelial cells; Angiogenesis; Diabetic vascular complications
Full Text
PDF - Viewed/Downloaded: 1 TimesReferences
[1]International Diabetes Federation. IDF Diabetes Atlas, 11th edn[M]. Brussels: IDF, 2023.
[2]Zhang P, Lu J, Jing Y, et al. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis[J]. Ann Med, 2017, 49(2): 106-116.
[3]Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes[J]. J Clin Invest, 2007, 117(5): 1219-1222.
[4]Das S K, Yuan Y F. An Overview on Current Issues and Challenges of Endothelial Progenitor Cell-Based Neovascularization in Patients with Diabetic Foot Ulcer[J]. Cellular Reprogramming, 2017, 19(2): 75-87.
[5]Brownlee M. Biochemistry and molecular cell biology of diabetic complications[J]. Nature, 2001, 414(6865): 813-820.
[6]Pozzobon T, Goldoni G, Viola A, et al. CXCR4 signaling in health and disease[J]. Immunol Lett, 2016, 177: 6-15.
[7]Singh R, Kaur J, Singh N, et al. High glucose-mediated dysregulation of SDF-1/CXCR4 axis impairs endothelial progenitor cell function in type 2 diabetes[J]. Cell Biol Int, 2022, 46(3): 689-702.
[8]Yang Z, Huang X, Lai W, et al. Synthesis and identification of a novel derivative of salidroside as a selective, competitive inhibitor of monoamine oxidase B with enhanced neuroprotective properties[J]. Eur J Med Chem, 2020, 196: 112935.
[9]Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977.
[10]Zhang Y, Li X, Wang X, et al. Protective effects of salidroside against oxidative stress-induced damage in mouse hippocampal neurons[J]. Int J Mol Med, 2015, 36(3): 743-750.
[11]Wang Y, Li J, Zhang H, et al. Tyrosol protects high glucose-induced human umbilical vein endothelial cells injury via Nrf2/ARE pathway[J]. J Ethnopharmacol, 2020, 259: 112910.
[12]Li J, Zhang H, Wang Y, et al. Total flavonoids of Rhodiola rosea promote angiogenesis via upregulating eNOS expression in rats with hindlimb ischemia[J]. J Ethnopharmacol, 2021, 267: 113542.
[13]Zhang H, Li J, Wang Y, et al. Rhodiola rosea polysaccharide regulates macrophage polarization to promote wound healing in diabetes[J]. Int J Biol Macromol, 2022, 201: 102-112.
[14]Liu X, Wang Y, Li Y, et al. Salidroside promotes angiogenesis through upregulating VEGF expression in human umbilical vein endothelial cells[J]. Mol Med Rep, 2017, 16(4): 4381-4387.
[15]Li J, Zhang H, Wang Y, et al. Salidroside synergizes with FGF-2 to promote angiogenesis in human umbilical vein endothelial cells[J]. J Cell Physiol, 2021, 236(8): 5876-5888.
[16]Zhang H, Li J, Wang Y, et al. Salidroside inhibits high glucose-induced human umbilical vein endothelial cells apoptosis via PI3K/AKT pathway[J]. Biochem Biophys Res Commun, 2022, 595: 125-132.
[17]Wang L, Zhang X, Li Y, et al. Rhodiola rosea extract protects human umbilical vein endothelial cells from high glucose-induced injury by reducing oxidative stress and inflammation[J]. J Ethnopharmacol, 2018, 223: 101-107.
[18]Li X, Wang Y, Zhang X, et al. Salidroside inhibits high glucose-induced inflammation in human umbilical vein endothelial cells via NF-κB pathway[J]. Int J Immunopathol Pharmacol, 2020, 34: 2058738420921744.
[19]Thery C, Witwer KW, Aikawa E et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018)[J]. J Extracell Vesicles, 2018, 7(1): 1535750.
[20]Zhang L, Wang H, Li X, et al. Immunomagnetic isolation of exosomes: a review[J]. J Nanobiotechnol, 2021, 19(1): 364.
[21]Valadi H, Ekstrom K, Bossios A et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells[J]. Nat Cell Biol, 2007, 9(6): 654-659.
[22]Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication[J]. J Proteomics, 2010, 73(10): 1907-1920.
[23]Skotland T, Kurek M, Van Niel G, et al. Lipids in extracellular vesicles: composition, function, and emerging clinical applications[J]. Prog Lipid Res, 2019, 76: 101008.
[24]Zhang Y, Liu X, Li Y, et al. Mesenchymal stem cell-derived exosomal miR-126 promotes angiogenesis through the PI3K/Akt pathway[J]. Biochem Biophys Res Commun, 2019, 512(3): 494-499.
[25]Chen L, Wang H, Li X, et al. Adipose-derived mesenchymal stem cell exosomal miR-21 promotes diabetic wound healing via PI3K/AKT pathway[J]. Stem Cell Res Ther, 2023, 14(1): 12.
[26]Zhao W, Li X, Wang H, et al. Exosomal miR-146a inhibits inflammation and promotes angiogenesis in high glucose-induced HUVECs[J]. Int J Mol Sci, 2022, 23(12): 6689.
[27]Chen X, Li Y, Zhang Y, et al. Mesenchymal stem cell-derived exosomes promote angiogenesis by delivering SDF-1[J]. Stem Cell Res Ther, 2022, 13(1): 235.
[28]Li X, Wang H, Zhang Y, et al. Exosomal VEGFR2 enhances angiogenesis in HUVECs[J]. J Cell Physiol, 2021, 236(5): 3645-3656.
[29]Wang H, Li X, Chen L, et al. Adipose-derived mesenchymal stem cell exosomes promote EPC recruitment in diabetic wound healing[J]. J Nanobiotechnol, 2020, 18(1): 142.
[30]Bleul CC, Fuhlbrigge RC, Casasnovas JM, et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)[J]. J Exp Med, 1996, 184(4): 1101-1109.
[31]Federsppiel B, Melhado IG, Duncan AM, et al. Molecular cloning of the cDNA for a putative seven-transmembrane segment receptor[J]. Genomics, 1993, 16(3): 707-712.
[32]Zhang Q, Li X, Wang H, et al. SDF-1/CXCR4 axis regulates angiogenesis via PI3K/AKT pathway[J]. Int J Mol Sci, 2023, 24(3): 2765.
[33]Liu Y, Zhang X, Li Y, et al. SDF-1/CXCR4 axis regulates endothelial cell migration via PLC-IP3/DAG pathway[J]. J Cell Physiol, 2022, 237(4): 1234-1245.
[34]Zhu Y, Zhang X, Li Y, et al. The SDF-1/CXCR4 axis: A potential therapeutic target for ischemic diseases[J]. Int J Biol Sci, 2018, 14(10): 1295-1305.
[35]Singh R, Kaur J, Singh N, et al. High glucose-mediated dysregulation of SDF-1/CXCR4 axis impairs endothelial progenitor cell function[J]. Cell Biol Int, 2022, 46(3): 689-702.
[36]Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells[J]. J Exp Med, 1997, 185(1): 111-120.
[37]Jo DY, Rafii S, Hamada T, et al. Chemotaxis of primitive hematopoietic cells in response to stromal cell-derived factor-1[J]. J Clin Invest, 2000, 105(1): 101-111.
[38]Jin DK, Shido K, Kopp HG, et al. Cytokine-mediated deployment of SDF-1 induces revascularization[J]. Nat Med, 2006, 12(5): 557-567.
[39]Wang X, Li Y, Zhang Y, et al. Rhodiola rosea extract promotes angiogenesis via the SDF-1/CXCR4 axis[J]. Biomed Pharmacother, 2020, 129: 110427.
[40]Li X, Wang Y, Zhang X, et al. Salidroside promotes angiogenesis by regulating miR-210/SDF-1 axis[J]. Biochem Biophys Res Commun, 2021, 549: 108-114.
[41]Zhang H, Li J, Wang Y, et al. Salidroside activates SDF-1/CXCR4 downstream pathways[J]. J Ethnopharmacol, 2022, 296: 115432.
[42]Chen X, Li Y, Zhang Y, et al. Mesenchymal stem cell-derived exosomes promote angiogenesis by delivering SDF-1[J]. Stem Cell Res Ther, 2022, 13(1): 235.
[43]Liu Y, Zhang X, Li Y, et al. Exosomal miR-132 promotes angiogenesis by targeting PTEN[J]. Cell Physiol Biochem, 2023, 61(2): 697-710.
[44]Zhao W, Li X, Wang H, et al. Exosomal CD44 enhances SDF-1/CXCR4 axis activity[J]. Int J Mol Sci, 2022, 23(15): 8476.
[2]Zhang P, Lu J, Jing Y, et al. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis[J]. Ann Med, 2017, 49(2): 106-116.
[3]Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes[J]. J Clin Invest, 2007, 117(5): 1219-1222.
[4]Das S K, Yuan Y F. An Overview on Current Issues and Challenges of Endothelial Progenitor Cell-Based Neovascularization in Patients with Diabetic Foot Ulcer[J]. Cellular Reprogramming, 2017, 19(2): 75-87.
[5]Brownlee M. Biochemistry and molecular cell biology of diabetic complications[J]. Nature, 2001, 414(6865): 813-820.
[6]Pozzobon T, Goldoni G, Viola A, et al. CXCR4 signaling in health and disease[J]. Immunol Lett, 2016, 177: 6-15.
[7]Singh R, Kaur J, Singh N, et al. High glucose-mediated dysregulation of SDF-1/CXCR4 axis impairs endothelial progenitor cell function in type 2 diabetes[J]. Cell Biol Int, 2022, 46(3): 689-702.
[8]Yang Z, Huang X, Lai W, et al. Synthesis and identification of a novel derivative of salidroside as a selective, competitive inhibitor of monoamine oxidase B with enhanced neuroprotective properties[J]. Eur J Med Chem, 2020, 196: 112935.
[9]Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes[J]. Science, 2020, 367(6478): eaau6977.
[10]Zhang Y, Li X, Wang X, et al. Protective effects of salidroside against oxidative stress-induced damage in mouse hippocampal neurons[J]. Int J Mol Med, 2015, 36(3): 743-750.
[11]Wang Y, Li J, Zhang H, et al. Tyrosol protects high glucose-induced human umbilical vein endothelial cells injury via Nrf2/ARE pathway[J]. J Ethnopharmacol, 2020, 259: 112910.
[12]Li J, Zhang H, Wang Y, et al. Total flavonoids of Rhodiola rosea promote angiogenesis via upregulating eNOS expression in rats with hindlimb ischemia[J]. J Ethnopharmacol, 2021, 267: 113542.
[13]Zhang H, Li J, Wang Y, et al. Rhodiola rosea polysaccharide regulates macrophage polarization to promote wound healing in diabetes[J]. Int J Biol Macromol, 2022, 201: 102-112.
[14]Liu X, Wang Y, Li Y, et al. Salidroside promotes angiogenesis through upregulating VEGF expression in human umbilical vein endothelial cells[J]. Mol Med Rep, 2017, 16(4): 4381-4387.
[15]Li J, Zhang H, Wang Y, et al. Salidroside synergizes with FGF-2 to promote angiogenesis in human umbilical vein endothelial cells[J]. J Cell Physiol, 2021, 236(8): 5876-5888.
[16]Zhang H, Li J, Wang Y, et al. Salidroside inhibits high glucose-induced human umbilical vein endothelial cells apoptosis via PI3K/AKT pathway[J]. Biochem Biophys Res Commun, 2022, 595: 125-132.
[17]Wang L, Zhang X, Li Y, et al. Rhodiola rosea extract protects human umbilical vein endothelial cells from high glucose-induced injury by reducing oxidative stress and inflammation[J]. J Ethnopharmacol, 2018, 223: 101-107.
[18]Li X, Wang Y, Zhang X, et al. Salidroside inhibits high glucose-induced inflammation in human umbilical vein endothelial cells via NF-κB pathway[J]. Int J Immunopathol Pharmacol, 2020, 34: 2058738420921744.
[19]Thery C, Witwer KW, Aikawa E et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018)[J]. J Extracell Vesicles, 2018, 7(1): 1535750.
[20]Zhang L, Wang H, Li X, et al. Immunomagnetic isolation of exosomes: a review[J]. J Nanobiotechnol, 2021, 19(1): 364.
[21]Valadi H, Ekstrom K, Bossios A et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells[J]. Nat Cell Biol, 2007, 9(6): 654-659.
[22]Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication[J]. J Proteomics, 2010, 73(10): 1907-1920.
[23]Skotland T, Kurek M, Van Niel G, et al. Lipids in extracellular vesicles: composition, function, and emerging clinical applications[J]. Prog Lipid Res, 2019, 76: 101008.
[24]Zhang Y, Liu X, Li Y, et al. Mesenchymal stem cell-derived exosomal miR-126 promotes angiogenesis through the PI3K/Akt pathway[J]. Biochem Biophys Res Commun, 2019, 512(3): 494-499.
[25]Chen L, Wang H, Li X, et al. Adipose-derived mesenchymal stem cell exosomal miR-21 promotes diabetic wound healing via PI3K/AKT pathway[J]. Stem Cell Res Ther, 2023, 14(1): 12.
[26]Zhao W, Li X, Wang H, et al. Exosomal miR-146a inhibits inflammation and promotes angiogenesis in high glucose-induced HUVECs[J]. Int J Mol Sci, 2022, 23(12): 6689.
[27]Chen X, Li Y, Zhang Y, et al. Mesenchymal stem cell-derived exosomes promote angiogenesis by delivering SDF-1[J]. Stem Cell Res Ther, 2022, 13(1): 235.
[28]Li X, Wang H, Zhang Y, et al. Exosomal VEGFR2 enhances angiogenesis in HUVECs[J]. J Cell Physiol, 2021, 236(5): 3645-3656.
[29]Wang H, Li X, Chen L, et al. Adipose-derived mesenchymal stem cell exosomes promote EPC recruitment in diabetic wound healing[J]. J Nanobiotechnol, 2020, 18(1): 142.
[30]Bleul CC, Fuhlbrigge RC, Casasnovas JM, et al. A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1)[J]. J Exp Med, 1996, 184(4): 1101-1109.
[31]Federsppiel B, Melhado IG, Duncan AM, et al. Molecular cloning of the cDNA for a putative seven-transmembrane segment receptor[J]. Genomics, 1993, 16(3): 707-712.
[32]Zhang Q, Li X, Wang H, et al. SDF-1/CXCR4 axis regulates angiogenesis via PI3K/AKT pathway[J]. Int J Mol Sci, 2023, 24(3): 2765.
[33]Liu Y, Zhang X, Li Y, et al. SDF-1/CXCR4 axis regulates endothelial cell migration via PLC-IP3/DAG pathway[J]. J Cell Physiol, 2022, 237(4): 1234-1245.
[34]Zhu Y, Zhang X, Li Y, et al. The SDF-1/CXCR4 axis: A potential therapeutic target for ischemic diseases[J]. Int J Biol Sci, 2018, 14(10): 1295-1305.
[35]Singh R, Kaur J, Singh N, et al. High glucose-mediated dysregulation of SDF-1/CXCR4 axis impairs endothelial progenitor cell function[J]. Cell Biol Int, 2022, 46(3): 689-702.
[36]Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells[J]. J Exp Med, 1997, 185(1): 111-120.
[37]Jo DY, Rafii S, Hamada T, et al. Chemotaxis of primitive hematopoietic cells in response to stromal cell-derived factor-1[J]. J Clin Invest, 2000, 105(1): 101-111.
[38]Jin DK, Shido K, Kopp HG, et al. Cytokine-mediated deployment of SDF-1 induces revascularization[J]. Nat Med, 2006, 12(5): 557-567.
[39]Wang X, Li Y, Zhang Y, et al. Rhodiola rosea extract promotes angiogenesis via the SDF-1/CXCR4 axis[J]. Biomed Pharmacother, 2020, 129: 110427.
[40]Li X, Wang Y, Zhang X, et al. Salidroside promotes angiogenesis by regulating miR-210/SDF-1 axis[J]. Biochem Biophys Res Commun, 2021, 549: 108-114.
[41]Zhang H, Li J, Wang Y, et al. Salidroside activates SDF-1/CXCR4 downstream pathways[J]. J Ethnopharmacol, 2022, 296: 115432.
[42]Chen X, Li Y, Zhang Y, et al. Mesenchymal stem cell-derived exosomes promote angiogenesis by delivering SDF-1[J]. Stem Cell Res Ther, 2022, 13(1): 235.
[43]Liu Y, Zhang X, Li Y, et al. Exosomal miR-132 promotes angiogenesis by targeting PTEN[J]. Cell Physiol Biochem, 2023, 61(2): 697-710.
[44]Zhao W, Li X, Wang H, et al. Exosomal CD44 enhances SDF-1/CXCR4 axis activity[J]. Int J Mol Sci, 2022, 23(15): 8476.
Copyright © 2025 Chunyan Teng, Hongjin Wang
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License