Calcineurin-nuclear Factor for Activated T Cells (NFAT) Signaling in Pathophysiology of Wound Healing

Overview

Journal Inflamm Regen

Publisher Biomed Central

Date 2021 Aug 19

PMID 34407893

Citations 3

Authors

Takahiro Manabe

Heamin Park

Takashi Minami

Affiliations

Soon will be listed here.

Abstract

Wound healing occurred with serial coordinated processes via coagulation-fibrinolysis, inflammation following to immune-activation, angiogenesis, granulation, and the final re-epithelization. Since the dermis forms critical physical and biological barriers, the repair system should be rapidly and accurately functioned to keep homeostasis in our body. The wound healing is impaired or dysregulated via an inappropriate microenvironment, which is easy to lead to several diseases, including fibrosis in multiple organs and psoriasis. Such a disease led to the dysregulation of several types of cells: immune cells, fibroblasts, mural cells, and endothelial cells. Moreover, recent progress in medical studies uncovers the significant concept. The calcium signaling, typically the following calcineurin-NFAT signaling, essentially regulates not only immune cell activations, but also various healing steps via coagulation, inflammation, and angiogenesis. In this review, we summarize the role of the NFAT activation pathway in wound healing and discuss its overall impact on future therapeutic ways.

Citing Articles

Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study.

Shetty R, Khamar P, Kannan R, Thacker P, Kumar N, Ghosh A Life (Basel). 2025; 15(2).

PMID: 40003656 PMC: 11856829. DOI: 10.3390/life15020246.

Biologic and Small Molecule Therapy in Atopic Dermatitis.

Shergill M, Bajwa B, Yilmaz O, Tailor K, Bouadi N, Mukovozov I Biomedicines. 2024; 12(8).

PMID: 39200305 PMC: 11351489. DOI: 10.3390/biomedicines12081841.

Modulation of calcium signaling and metabolic pathways in endothelial cells with magnetic fields.

Gorobets O, Gorobets S, Polyakova T, Zablotskii V Nanoscale Adv. 2024; 6(4):1163-1182.

PMID: 38356636 PMC: 10863714. DOI: 10.1039/d3na01065a.

The Pleiotropic Role of Extracellular ATP in Myocardial Remodelling.

Sudi S, Thomas F, Daud S, Daud D, Sunggip C Molecules. 2023; 28(5).

PMID: 36903347 PMC: 10004151. DOI: 10.3390/molecules28052102.

References

Eckes B, Zigrino P, Kessler D, Holtkotter O, Shephard P, Mauch C . Fibroblast-matrix interactions in wound healing and fibrosis. Matrix Biol. 2000; 19(4):325-32. DOI: 10.1016/s0945-053x(00)00077-9. View

Weller K, Foitzik K, Paus R, Syska W, Maurer M . Mast cells are required for normal healing of skin wounds in mice. FASEB J. 2006; 20(13):2366-8. DOI: 10.1096/fj.06-5837fje. View

Minami T, Yano K, Miura M, Kobayashi M, Suehiro J, Reid P . The Down syndrome critical region gene 1 short variant promoters direct vascular bed-specific gene expression during inflammation in mice. J Clin Invest. 2009; 119(8):2257-70. PMC: 2719921. DOI: 10.1172/JCI35738. View

Koh T, DiPietro L . Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med. 2011; 13:e23. PMC: 3596046. DOI: 10.1017/S1462399411001943. View

Gordon C, Rojavin Y, Patel M, Zins J, Grana G, Kann B . A review on bevacizumab and surgical wound healing: an important warning to all surgeons. Ann Plast Surg. 2009; 62(6):707-9. DOI: 10.1097/SAP.0b013e3181828141. View

Sauerhering L, Kupke A, Meier L, Dietzel E, Hoppe J, Gruber A . Cyclophilin inhibitors restrict Middle East respiratory syndrome coronavirus interferon-λ and in mice. Eur Respir J. 2020; 56(5). PMC: 7331652. DOI: 10.1183/13993003.01826-2019. View

Werner S, Krieg T, Smola H . Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 2007; 127(5):998-1008. DOI: 10.1038/sj.jid.5700786. View

Bochkov V, Mechtcheriakova D, Lucerna M, Huber J, Malli R, Graier W . Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT. Blood. 2002; 99(1):199-206. DOI: 10.1182/blood.v99.1.199. View

Gratuze M, Noel A, Julien C, Cisbani G, Milot-Rousseau P, Morin F . Tau hyperphosphorylation and deregulation of calcineurin in mouse models of Huntington's disease. Hum Mol Genet. 2014; 24(1):86-99. DOI: 10.1093/hmg/ddu456. View

10.

Alvarez O, Mertz P, Smerbeck R, Eaglstein W . The healing of superficial skin wounds is stimulated by external electrical current. J Invest Dermatol. 1983; 81(2):144-8. DOI: 10.1111/1523-1747.ep12543498. View

11.

Moloney F, Keane S, OKelly P, Conlon P, Murphy G . The impact of skin disease following renal transplantation on quality of life. Br J Dermatol. 2005; 153(3):574-8. DOI: 10.1111/j.1365-2133.2005.06699.x. View

12.

Darby I, Hewitson T . Fibroblast differentiation in wound healing and fibrosis. Int Rev Cytol. 2007; 257:143-79. DOI: 10.1016/S0074-7696(07)57004-X. View

13.

Min Y, Mo Q, Wang J, Deng F, Wang H, Ning Y . SARS-CoV-2 nsp1: Bioinformatics, Potential Structural and Functional Features, and Implications for Drug/Vaccine Designs. Front Microbiol. 2020; 11:587317. PMC: 7550470. DOI: 10.3389/fmicb.2020.587317. View

14.

Bayat M, Asgari-Moghadam Z, Maroufi M, Rezaie F, Bayat M, Rakhshan M . Experimental wound healing using microamperage electrical stimulation in rabbits. J Rehabil Res Dev. 2006; 43(2):219-26. DOI: 10.1682/jrrd.2005.05.0089. View

15.

Yano K, Okada Y, Beldi G, Shih S, Bodyak N, Okada H . Elevated levels of placental growth factor represent an adaptive host response in sepsis. J Exp Med. 2008; 205(11):2623-31. PMC: 2571936. DOI: 10.1084/jem.20080398. View

16.

Lin C, Park T, Chen Z, Leavitt J . Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells. J Biol Chem. 1993; 268(4):2781-92. View

17.

Deodhar A, Rana R . Surgical physiology of wound healing: a review. J Postgrad Med. 1997; 43(2):52-6. View

18.

Ruthenborg R, Ban J, Wazir A, Takeda N, Kim J . Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1. Mol Cells. 2014; 37(9):637-43. PMC: 4179131. DOI: 10.14348/molcells.2014.0150. View

19.

Minami T . Calcineurin-NFAT activation and DSCR-1 auto-inhibitory loop: how is homoeostasis regulated?. J Biochem. 2014; 155(4):217-26. DOI: 10.1093/jb/mvu006. View

20.

Zhang Z, Nie F, Kang C, Chen B, Qin Z, Ma J . Increased periostin expression affects the proliferation, collagen synthesis, migration and invasion of keloid fibroblasts under hypoxic conditions. Int J Mol Med. 2014; 34(1):253-61. DOI: 10.3892/ijmm.2014.1760. View