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Cited by 42Wound Healing and TreatmentsImmune cells in cancerMacrophage Migration Inhibitory Factor

AKT3 deficiency in M2 macrophages impairs cutaneous wound healing by disrupting tissue remodeling

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Gu, Song, Dai, Hanhao, Zhao, Xilian, Gui, Chang, Gui, Jianchao·2020·Aging
DOI 10.18632/aging.103051PMC PMC7202485
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Abstract

mice had an impaired ability to promote wound healing. Thus, the downregulation of AKT3 in M2 macrophages prolonged tissue remodeling and delayed cutaneous wound healing.

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  1. [1]Lazarus GS, Cooper DM, Knighton DR, Margolis DJ, Pecoraro RE, Rodeheaver G, Robson MC. Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994; 130: 489– 93. 10.1001/archderm.1994.01690040093015 8166487 · DOI
  2. [2]Mostow EN. Diagnosis and classification of chronic wounds. Clin Dermatol. 1994; 12: 3– 9. 10.1016/0738-081x(94)90251-8 8180943 · DOI
  3. [3]Mustoe TA, O'Shaughnessy K, Kloeters O. Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg. 2006; 117: 35S– 41S. 10.1097/01.prs.0000225431.63010.1b 16799373 · DOI · Paper page
  4. [4]Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med. 2014; 20: 857– 69. 10.1038/nm.3653 25100531 · DOI
  5. [5]Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016; 44: 450– 62. 10.1016/j.immuni.2016.02.015 26982353 PMC4794754 · DOI · Paper page
  6. [6]Ho J, Walsh C, Yue D, Dardik A, Cheema U. Current Advancements and Strategies in Tissue Engineering for Wound Healing: A Comprehensive Review. Adv Wound Care (New Rochelle). 2017; 6: 191– 209. 10.1089/wound.2016.0723 28616360 PMC5467128 · DOI
  7. [7]Raghow R. The role of extracellular matrix in postinflammatory wound healing and fibrosis. FASEB J. 1994; 8: 823– 31. 10.1096/fasebj.8.11.8070631 8070631 · DOI · Paper page
  8. [8]Godwin JW, Pinto AR, Rosenthal NA. Chasing the recipe for a pro-regenerative immune system. Semin Cell Dev Biol. 2017; 61: 71– 79. 10.1016/j.semcdb.2016.08.008 27521522 PMC5338634 · DOI
  9. [10]Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8: 958– 69. 10.1038/nri2448 19029990 PMC2724991 · DOI · Paper page
  10. [11]Zhang Y, Desai A, Yang SY, Bae KB, Antczak MI, Fink SP, Tiwari S, Willis JE, Williams NS, Dawson DM, Wald D, Chen WD, Wang Z, et al. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science. 2015; 348: aaa2340. 10.1126/science.aaa2340 26068857 PMC4481126 · DOI
  11. [12]Peiseler M, Kubes P. Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair. Eur J Trauma Emerg Surg. 2018; 44: 335– 49. 10.1007/s00068-018-0956-1 29666944 · DOI
  12. [14]Patel U, Rajasingh S, Samanta S, Cao T, Dawn B, Rajasingh J. Macrophage polarization in response to epigenetic modifiers during infection and inflammation. Drug Discovery Today. 2017; 22: 186– 93. 10.1016/j.drudis.2016.08.006 27554801 PMC5226865 · DOI
  13. [16]Happle C, Lachmann N, Škuljec J, Wetzke M, Ackermann M, Brennig S, Mucci A, Jirmo AC, Groos S, Mirenska A, Hennig C, Rodt T, Bankstahl JP, et al. Pulmonary transplantation of macrophage progenitors as effective and long-lasting therapy for hereditary pulmonary alveolar proteinosis. Sci Transl Med. 2014; 6: 250ra113. 10.1126/scitranslmed.3009750 25143363 · DOI
  14. [17]Clark RA, Pavlis M. Dysregulation of the mTOR pathway secondary to mutations or a hostile microenvironment contributes to cancer and poor wound healing. J Invest Dermatol. 2009; 129: 529– 31. 10.1038/jid.2008.441 19209152 · DOI
  15. [18]Xu KP, Li Y, Ljubimov AV, Yu FS. High glucose suppresses epidermal growth factor receptor/phosphatidylinositol 3-kinase/Akt signaling pathway and attenuates corneal epithelial wound healing. Diabetes. 2009; 58: 1077– 85. 10.2337/db08-0997 19188434 PMC2671049 · DOI
  16. [19]Cheung M, Testa JR. Diverse mechanisms of AKT pathway activation in human malignancy. Curr Cancer Drug Targets. 2013; 13: 234– 44. 10.2174/1568009611313030002 23297823 PMC3678724 · DOI
  17. [20]Song G, Ouyang G, Bao S. The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 2005; 9: 59– 71. 10.1111/j.1582-4934.2005.tb00337.x 15784165 PMC6741304 · DOI
  18. [21]Hinz N, Jücker M. Distinct functions of AKT isoforms in breast cancer: a comprehensive review. Cell Commun Signal. 2019; 17: 154. 10.1186/s12964-019-0450-3 31752925 PMC6873690 · DOI
  19. [22]Chin YR, Toker A. Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer. Cell Signal. 2009; 21: 470– 6. 10.1016/j.cellsig.2008.11.015 19110052 PMC2719559 · DOI
  20. [23]Cai L, Liu X, Guo Q, Huang Q, Zhang Q, Cao Z. MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy. Genes Genomics. 2020; 42: 77– 85. 10.1007/s13258-019-00881-z 31736006 · DOI
  21. [24]Shi F, Deng Z, Zhou Z, Jiang CY, Zhao RZ, Sun F, Cui D, Bei XY, Yang BY, Sun Q, Wang XJ, Wu Q, Xia SJ, Han BM. QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling. J Cell Mol Med. 2019; 23: 6578– 94. 10.1111/jcmm.14481 31449345 PMC6787450 · DOI
  22. [25]Ding L, Biswas S, Morton RE, Smith JD, Hay N, Byzova TV, Febbraio M, Podrez EA. Akt3 deficiency in macrophages promotes foam cell formation and atherosclerosis in mice. Cell Metab. 2012; 15: 861– 72. 10.1016/j.cmet.2012.04.020 22632897 PMC3372639 · DOI · Paper page
  23. [27]Midwood KS, Williams LV, Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol. 2004; 36: 1031– 7. 10.1016/j.biocel.2003.12.003 15094118 · DOI · Paper page
  24. [28]Shi F, Deng Z, Zhou Z, Jiang B, Jiang CY, Zhao RZ, Sun F, Cui D, Sun MH, Sun Q, Wang XJ, Wu Q, Xia SJ, Han BM. Heat injured stromal cells-derived exosomal EGFR enhances prostatic wound healing after thulium laser resection through EMT and NF-κB signaling. Prostate. 2019; 79: 1238– 55. 10.1002/pros.23827 31124594 · DOI
  25. [29]Otterço AN, Andrade AL, Brassolatti P, Pinto KNZ, Araújo HSS, Parizotto NA. Photobiomodulation mechanisms in the kinetics of the wound healing process in rats. J Photochem Photobiol B. 2018; 183: 22– 29. 10.1016/j.jphotobiol.2018.04.010 29684717 · DOI
  26. [30]Gumel AM, Razaif-Mazinah MR, Anis SN, Annuar MS. Poly (3-hydroxyalkanoates)-co-(6-hydroxyhexanoate) hydrogel promotes angiogenesis and collagen deposition during cutaneous wound healing in rats. Biomed Mater. 2015; 10: 045001. 10.1088/1748-6041/10/4/045001 26154416 · DOI
  27. [31]Kaunitz H. Cholesterol metabolism and tissue repair in arteriosclerosis. Proc Rudolf Virchow Med Soc City N Y. 1970–1971; 28: 57– 64. 5293519
  28. [32]Paluch EK, Aspalter IM, Sixt M. Focal Adhesion-Independent Cell Migration. Annu Rev Cell Dev Biol. 2016; 32: 469– 90. 10.1146/annurev-cellbio-111315-125341 27501447 · DOI
  29. [33]Zhou T, Yang Z, Chen Y, Chen Y, Huang Z, You B, Peng Y, Chen J. Estrogen Accelerates Cutaneous Wound Healing by Promoting Proliferation of Epidermal Keratinocytes via Erk/Akt Signaling Pathway. Cell Physiol Biochem. 2016; 38: 959– 68. 10.1159/000443048 26938432 · DOI
  30. [34]Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999; 341: 738– 46. 10.1056/NEJM199909023411006 10471461 · DOI · Paper page
  31. [35]Parfejevs V, Debbache J, Shakhova O, Schaefer SM, Glausch M, Wegner M, Suter U, Riekstina U, Werner S, Sommer L. Injury-activated glial cells promote wound healing of the adult skin in mice. Nat Commun. 2018; 9: 236. 10.1038/s41467-017-01488-2 29339718 PMC5770460 · DOI
  32. [36]Nguyen CM, Tartar DM, Bagood MD, So M, Nguyen AV, Gallegos A, Fregoso D, Serrano J, Nguyen D, Degovics D, Adams A, Harouni B, Fuentes JJ, Gareau MG, Crawford RW, Soulika AM, Isseroff RR. Topical Fluoxetine as a Novel Therapeutic That Improves Wound Healing in Diabetic Mice. Diabetes. 2019; 68: 1499– 1507. 10.2337/db18-1146 31048368 PMC6609984 · DOI
  33. [37]Cheng TL, Chen PK, Huang WK, Kuo CH, Cho CF, Wang KC, Shi GY, Wu HL, Lai CH. Plasminogen/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing. J Mol Med (Berl). 2018; 96: 1333– 44. 10.1007/s00109-018-1702-1 30341568 · DOI
  34. [38]Haensel D, Dai X. Epithelial-to-mesenchymal transition in cutaneous wound healing: Where we are and where we are heading. Dev Dyn. 2018; 247: 473– 80. 10.1002/dvdy.24561 28795450 PMC5809211 · DOI · Paper page
  35. [39]Rousselle P, Braye F, Dayan G. Re-epithelialization of adult skin wounds: Cellular mechanisms and therapeutic strategies. Adv Drug Deliv Rev. 2019; 146: 344– 65. 10.1016/j.addr.2018.06.019 29981800 · DOI
  36. [40]Lohmann N, Schirmer L, Atallah P, Wandel E, Ferrer RA, Werner C, Simon JC, Franz S, Freudenberg U. Glycosaminoglycan-based hydrogels capture inflammatory chemokines and rescue defective wound healing in mice. Sci Transl Med. 2017; 9. 10.1126/scitranslmed.aai9044 28424334 · DOI
  37. [41]Zhang LL, Zhang LF, Shi YB. Down-regulated paxillin suppresses cell proliferation and invasion by inhibiting M2 macrophage polarization in colon cancer. Biol Chem. 2018; 399: 1285– 95. 10.1515/hsz-2018-0002 29924724 · DOI
  38. [42]Andrulewicz-Botulińska E, Kuźmicz I, Nazaruk J, Wosek J, Galicka A. The concentration-dependent effect of anethole on collagen, MMP-2 and GAG in human skin fibroblast cultures. Adv Med Sci. 2019; 64: 111– 116. 10.1016/j.advms.2018.08.008 30640076 · DOI
  39. [43]Chan JJ, Tan TJY, Dent RA. Novel therapeutic avenues in triple-negative breast cancer: PI3K/AKT inhibition, androgen receptor blockade, and beyond. Ther Adv Med Oncol. 2019; 11. 10.1177/1758835919880429 31636720 PMC6785914 · DOI
  40. [44]Marques RB, Aghai A, de Ridder CMA, Stuurman D, Hoeben S, Boer A, Ellston RP, Barry ST, Davies BR, Trapman J, van Weerden WM. High Efficacy of Combination Therapy Using PI3K/AKT Inhibitors with Androgen Deprivation in Prostate Cancer Preclinical Models. Eur Urol. 2015; 67: 1177– 85. 10.1016/j.eururo.2014.08.053 25220373 · DOI
  41. [45]Chang C, Yeh S, Lee SO, Chang TM. Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells. Nucl Recept Signal. 2013; 11: e001. 10.1621/nrs.11001 24653668 PMC3960937 · DOI
  42. [46]Mukai K, Nakajima Y, Asano K, Nakatani T. Topical estrogen application to wounds promotes delayed cutaneous wound healing in 80-week-old female mice. PLoS One. 2019; 14: e0225880. 10.1371/journal.pone.0225880 31774863 PMC6881033 · DOI
  43. [47]Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, Sundararajan D, Chen WS, Crawford SE, Coleman KG, Hay N. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 2003; 17: 1352– 65. 10.1101/gad.1089403 12782654 PMC196068 · DOI
  44. [48]Hay N. Akt isoforms and glucose homeostasis - the leptin connection. Trends Endocrinol Metab. 2011; 22: 66– 73. 10.1016/j.tem.2010.09.003 20947368 PMC3427792 · DOI
  45. [49]Turner KM, Sun Y, Ji P, Granberg KJ, Bernard B, Hu L, Cogdell DE, Zhou X, Yli-Harja O, Nykter M, Shmulevich I, Yung WK, Fuller GN, Zhang W. Genomically amplified Akt3 activates DNA repair pathway and promotes glioma progression. Proc Natl Acad Sci U S A. 2015; 112: 3421– 6. 10.1073/pnas.1414573112 25737557 PMC4371922 · DOI
  46. [50]Deng Z, Shi F, Zhou Z, Sun F, Sun MH, Sun Q, Chen L, Li D, Jiang CY, Zhao RZ, Cui D, Wang XJ, Jing YF, et al. M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo. Toxicol Appl Pharmacol. 2019; 366: 83– 95. 10.1016/j.taap.2019.01.022 30690042 · DOI

Cited by

Sorted by citations

Authors
Gu, S., Dai, H., Zhao, X., Gui, C., & Gui, J.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Nanjing First Hospital (CN)
  • Washington University in St. Louis (US)
Corresponding author
Gui, Jianchao
ORCID
Venue
Aging
Publisher
Impact Journals, LLC
Published
2020-04-14
Volume
12
Issue
8
Pages
6928-6946
ISSN
1945-4589 (ISSN-L)
DOI
10.18632/aging.103051
PMC
PMC7202485
OpenAlex
W3015724188
Cited by
42
References
5
Citations by year
2026: 7 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 5
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Aging (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Macrophage Migration Inhibitory Factor
Keywords
AKT3, M2 macrophages, skin wound healing, tissue remodeling, macrophage polarization
MeSH terms
Collagen Type I, alpha 1 Chain, CD68 Molecule, Animals, Cell Line, Cell Movement, Extracellular Matrix, Fibroblasts, Humans, Macrophages, Membrane Glycoproteins, Receptors, Immunologic, RNA, Messenger, Skin, Skin Physiological Phenomena, Wound Healing, Wounds and Injuries, Antigens, Differentiation, Myelomonocytic, Signal Transduction, Down-Regulation, Antigens, CD, Mice, Knockout, Coculture Techniques, Collagen Type I, Collagen Type XI, Cell Proliferation, Proto-Oncogene Proteins c-akt, Mice, Gene Knockdown Techniques

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