
Journal of Shanghai Jiao Tong University (Medical Science) ›› 2025, Vol. 45 ›› Issue (6): 792-799.doi: 10.3969/j.issn.1674-8115.2025.06.015
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HUANG Yinghe1, ZHAO Guanyu1, SUN Yang1, HOU Jianji1, ZUO Yong1,2(
)
Received:2025-02-24
Accepted:2025-03-26
Online:2025-06-23
Published:2025-06-23
Contact:
ZUO Yong
E-mail:zuoyong@shsmu.edu.cn
Supported by:CLC Number:
HUANG Yinghe, ZHAO Guanyu, SUN Yang, HOU Jianji, ZUO Yong. Research progress on macrophage metabolic regulation in wound healing of diabetes mellitus type 2[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(6): 792-799.
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| [1] | FREEDMAN B R, HWANG C, TALBOT S, et al. Breakthrough treatments for accelerated wound healing[J]. Sci Adv, 2023, 9(20): eade7007. |
| [2] | YU F X, LEE P S Y, YANG L L, et al. The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas[J]. Prog Retin Eye Res, 2022, 89: 101039. |
| [3] | KAUSHIK K, DAS A. TWIST1-reprogrammed endothelial cell transplantation potentiates neovascularization-mediated diabetic wound tissue regeneration[J]. Diabetes, 2020, 69(6): 1232-1247. |
| [4] | GUO W, QIU W, AO X, et al. Low-concentration DMSO accelerates skin wound healing by Akt/mTOR-mediated cell proliferation and migration in diabetic mice[J]. Br J Pharmacol, 2020, 177(14): 3327-3341. |
| [5] | SHARIFIAGHDAM M, SHAABANI E, FARIDI-MAJIDI R, et al. Macrophages as a therapeutic target to promote diabetic wound healing[J]. Mol Ther, 2022, 30(9): 2891-2908. |
| [6] | WOLF S J, MELVIN W J, GALLAGHER K. Macrophage-mediated inflammation in diabetic wound repair[J]. Semin Cell Dev Biol, 2021, 119: 111-118. |
| [7] | ZHOU B S, MAGANA L, HONG Z G, et al. The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic-epigenetic reprogramming and resolves inflammatory injury[J]. Nat Immunol, 2020, 21(11): 1430-1443. |
| [8] | XIE J, WU X W, ZHENG S, et al. Aligned electrospun poly(L-lactide) nanofibers facilitate wound healing by inhibiting macrophage M1 polarization via the JAK-STAT and NF-κB pathways[J]. J Nanobiotechnology, 2022, 20(1): 342. |
| [9] | SHAN X, HU P H, NI L N, et al. Serine metabolism orchestrates macrophage polarization by regulating the IGF1-p38 axis[J]. Cell Mol Immunol, 2022, 19(11): 1263-1278. |
| [10] | AUDU C O, MELVIN W J, JOSHI A D, et al. Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair[J]. Cell Mol Immunol, 2022, 19(11): 1251-1262. |
| [11] | PEÑA O A, MARTIN P. Cellular and molecular mechanisms of skin wound healing[J]. Nat Rev Mol Cell Biol, 2024, 25(8): 599-616. |
| [12] | BRAZIL J C, QUIROS M, NUSRAT A, et al. Innate immune cell-epithelial crosstalk during wound repair[J]. J Clin Invest, 2019, 129(8): 2983-2993. |
| [13] | APAYDIN O, ALTAIKYZY A, FILOSA A, et al. Alpha-1 adrenergic signaling drives cardiac regeneration via extracellular matrix remodeling transcriptional program in zebrafish macrophages[J]. Dev Cell, 2023, 58(22): 2460-2476.e7. |
| [14] | REYNOLDS G, VEGH P, FLETCHER J, et al. Developmental cell programs are co-opted in inflammatory skin disease[J]. Science, 2021, 371(6527): eaba6500. |
| [15] | ZHAO P X, CAI Z S, ZHANG X J, et al. Hydrogen attenuates inflammation by inducing early M2 macrophage polarization in skin wound healing[J]. Pharmaceuticals (Basel), 2023, 16(6): 885. |
| [16] | RUNGRATANAWANICH W, QU Y, WANG X, et al. Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury[J]. Exp Mol Med, 2021, 53(2): 168-188. |
| [17] | WONG S L, DEMERS M, MARTINOD K, et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing[J]. Nat Med, 2015, 21(7): 815-819. |
| [18] | SONG J Y, ZHU K Y, WANG H P, et al. Deciphering the emerging role of programmed cell death in diabetic wound healing[J]. Int J Biol Sci, 2023, 19(15): 4989-5003. |
| [19] | LIU Y, LI Z N, LI W D, et al. Discovery of β-sitosterol's effects on molecular changes in rat diabetic wounds and its impact on angiogenesis and macrophages[J]. Int Immunopharmacol, 2024, 126: 111283. |
| [20] | ZHANG X Y, WU Y, GONG H, et al. A multifunctional herb-derived glycopeptide hydrogel for chronic wound healing[J]. Small, 2024, 20(36): e2400516. |
| [21] | ZHANG F X, SHAN S, FU C L, et al. Advanced mass spectrometry-based biomarker identification for metabolomics of diabetes mellitus and its complications[J]. Molecules, 2024, 29(11): 2530. |
| [22] | VAN DEN BOSSCHE J, BAARDMAN J, OTTO N A, et al. Mitochondrial dysfunction prevents repolarization of inflammatory macrophages[J]. Cell Rep, 2016, 17(3): 684-696. |
| [23] | PILLON N J, LOOS R J F, MARSHALL S M, et al. Metabolic consequences of obesity and type 2 diabetes: balancing genes and environment for personalized care[J]. Cell, 2021, 184(6): 1530-1544. |
| [24] | RUSSO S, KWIATKOWSKI M, GOVORUKHINA N, et al. Meta-inflammation and metabolic reprogramming of macrophages in diabetes and obesity: the importance of metabolites[J]. Front Immunol, 2021, 12: 746151. |
| [25] | EMING S A, MURRAY P J, PEARCE E J. Metabolic orchestration of the wound healing response[J]. Cell Metab, 2021, 33(9): 1726-1743. |
| [26] | MOUTON A J, LI X, HALL M E, et al. Obesity, hypertension, and cardiac dysfunction: novel roles of immunometabolism in macrophage activation and inflammation[J]. Circ Res, 2020, 126(6): 789-806. |
| [27] | BOUTENS L, HOOIVELD G J, DHINGRA S, et al. Unique metabolic activation of adipose tissue macrophages in obesity promotes inflammatory responses[J]. Diabetologia, 2018, 61(4): 942-953. |
| [28] | HE X T, LI X, ZHANG M, et al. Role of molybdenum in material immunomodulation and periodontal wound healing: targeting immunometabolism and mitochondrial function for macrophage modulation[J]. Biomaterials, 2022, 283: 121439. |
| [29] | WILLENBORG S, SANIN D E, JAIS A, et al. Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing[J]. Cell Metab, 2021, 33(12): 2398-2414.e9. |
| [30] | ZHANG D, TANG Z Y, HUANG H, et al. Metabolic regulation of gene expression by histone lactylation[J]. Nature, 2019, 574(7779): 575-580. |
| [31] | KOTWAL G J, CHIEN S F. Macrophage differentiation in normal and accelerated wound healing[J]. Results Probl Cell Differ, 2017, 62: 353-364. |
| [32] | HUANG F, LU X Y, YANG Y, et al. Microenvironment-based diabetic foot ulcer nanomedicine[J]. Adv Sci (Weinh), 2023, 10(2): e2203308. |
| [33] | LIN C W, HUNG C M, CHEN W J, et al. New horizons of macrophage immunomodulation in the healing of diabetic foot ulcers[J]. Pharmaceutics, 2022, 14(10): 2065. |
| [34] | YAO Y M, ZHANG H. Better therapy for combat injury[J]. Mil Med Res, 2019, 6(1): 23. |
| [35] | LI Q H, SONG H J, LI S Y, et al. Macrophage metabolism reprogramming EGCG-Cu coordination capsules delivered in polyzwitterionic hydrogel for burn wound healing and regeneration[J]. Bioact Mater, 2023, 29: 251-264. |
| [36] | ZHANG K, LU W C, ZHANG M, et al. Reducing host aldose reductase activity promotes neuronal differentiation of transplanted neural stem cells at spinal cord injury sites and facilitates locomotion recovery[J]. Neural Regen Res, 2022, 17(8): 1814-1820. |
| [37] | HE J B, ZHOU S S, WANG J X, et al. Anti-inflammatory and anti-oxidative electrospun nanofiber membrane promotes diabetic wound healing via macrophage modulation[J]. J Nanobiotechnology, 2024, 22(1): 116. |
| [38] | BATISTA-GONZALEZ A, VIDAL R, CRIOLLO A, et al. New insights on the role of lipid metabolism in the metabolic reprogramming of macrophages[J]. Front Immunol, 2020, 10: 2993. |
| [39] | LEE J H, PHELAN P, SHIN M, et al. SREBP-1a-stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1[J]. Proc Natl Acad Sci USA, 2018, 115(52): E12228-E12234. |
| [40] | VASSILIOU E, FARIAS-PEREIRA R. Impact of lipid metabolism on macrophage polarization: implications for inflammation and tumor immunity[J]. Int J Mol Sci, 2023, 24(15): 12032. |
| [41] | SHOOK B A, WASKO R R, MANO O, et al. Dermal adipocyte lipolysis and myofibroblast conversion are required for efficient skin repair[J]. Cell Stem Cell, 2020, 26(6): 880-895.e6. |
| [42] | COOPER P O, KLEB S S, NOONEPALLE S K, et al. G-protein-coupled receptor 84 regulates acute inflammation in normal and diabetic skin wounds[J]. Cell Rep, 2024, 43(6): 114288. |
| [43] | JETTEN N, ROUMANS N, GIJBELS M J, et al. Wound administration of M2-polarized macrophages does not improve murine cutaneous healing responses[J]. PLoS One, 2014, 9(7): e102994. |
| [44] | PERCIVAL S L, MCCARTY S, HUNT J A, et al. The effects of pH on wound healing, biofilms, and antimicrobial efficacy[J]. Wound Repair Regen, 2014, 22(2): 174-186. |
| [45] | OLONA A, HATELEY C, MURALIDHARAN S, et al. Sphingolipid metabolism during toll-like receptor 4 (TLR4)-mediated macrophage activation[J]. Br J Pharmacol, 2021, 178(23): 4575-4587. |
| [46] | HE L, WEBER K J, SCHILLING J D. Glutamine modulates macrophage lipotoxicity[J]. Nutrients, 2016, 8(4): 215. |
| [47] | PAN Y, HUI X Y, HOO R L C, et al. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation[J]. J Clin Invest, 2019, 129(2): 834-849. |
| [48] | CHI Z X, CHEN S, YANG D H, et al. Gasdermin D-mediated metabolic crosstalk promotes tissue repair[J]. Nature, 2024, 634(8036): 1168-1177. |
| [49] | DEBATS I G, WOLFS T M, GOTOH T, et al. Role of arginine in superficial wound healing in man[J]. Nitric Oxide, 2009, 21(3/4): 175-183. |
| [50] | ITO D, ITO H, IDETA T, et al. Systemic and topical administration of spermidine accelerates skin wound healing[J]. Cell Commun Signal, 2021, 19(1): 36. |
| [51] | ARRIBAS-LÓPEZ E, ZAND N, OJO O, et al. The effect of amino acids on wound healing: a systematic review and meta-analysis on arginine and glutamine[J]. Nutrients, 2021, 13(8): 2498. |
| [52] | LIU Y, SHI J P, XIONG W, et al. Production of an animal model of semi-Yin and semi-Yang syndrome with diabetic ulcers and study of its pathological and metabolic features[J]. Evid Based Complement Alternat Med, 2021, 2021: 6345147. |
| [53] | MANCHANDA M, TORRES M, INUOSSA F, et al. Metabolic reprogramming and reliance in human skin wound healing[J]. J Invest Dermatol, 2023, 143(10): 2039-2051.e10. |
| [54] | REN W K, XIA Y Y, CHEN S Y, et al. Glutamine metabolism in macrophages: a novel target for obesity/type 2 diabetes[J]. Adv Nutr, 2019, 10(2): 321-330. |
| [55] | LV D M, CAO X L, ZHONG L, et al. Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing[J]. Cell Rep Med, 2023, 4(8): 101129. |
| [56] | ZHAO M N, WANG K Y, LIN R, et al. Influence of glutamine metabolism on diabetes development: a scientometric review[J]. Heliyon, 2024, 10(4): e25258. |
| [57] | GIESBERTZ P, DANIEL H. Branched-chain amino acids as biomarkers in diabetes[J]. Curr Opin Clin Nutr Metab Care, 2016, 19(1): 48-54. |
| [58] | GAN Z D, GUO Y, ZHAO M Y, et al. Excitatory amino acid transporter supports inflammatory macrophage responses[J]. Sci Bull (Beijing), 2024, 69(15): 2405-2419. |
| [59] | YAN J L, TIE G D, WANG S Y, et al. Diabetes impairs wound healing by Dnmt1-dependent dysregulation of hematopoietic stem cells differentiation towards macrophages[J]. Nat Commun, 2018, 9(1): 33. |
| [60] | HOU Y X, WEI D, ZHANG Z Q, et al. Downregulation of nutrition sensor GCN2 in macrophages contributes to poor wound healing in diabetes[J]. Cell Rep, 2024, 43(1): 113658. |
| [61] | ZHANG Q Z, CHEN S Y, GUO Y, et al. Phenylalanine diminishes M1 macrophage inflammation[J]. Sci China Life Sci, 2023, 66(12): 2862-2876. |
| [62] | ZHU H T, XING C, DOU X Q, et al. Chiral hydrogel accelerates re-epithelization in chronic wounds via mechanoregulation[J]. Adv Healthc Mater, 2022, 11(21): e2201032. |
| [63] | MIAO M Y, NIU Y W, XIE T, et al. Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation[J]. Wound Repair Regen, 2012, 20(2): 203-213. |
| [64] | CHEN M, CHANG C, LEVIAN B, et al. Why are there so few FDA-approved therapeutics for wound healing?[J]. Int J Mol Sci, 2023, 24(20): 15109. |
| [65] | DA PORTO A, MIRANDA C, BROSOLO G, et al. Nutritional supplementation on wound healing in diabetic foot: what is known and what is new?[J]. World J Diabetes, 2022, 13(11): 940-948. |
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