Abstract
Wound inflammation occurs in response to injury. It is a coordinated process involving tissues, cells, and an array of soluble, cell-associated, and intracellular factors. The role of certain microRNAs in wound healing and inflammation, in particular (a key process underpinning wound healing), has emerged in recent years. Here, mechanisms involving inflammatory cells, secreted molecules, and miRNAs that can affect wound healing are reviewed. Of interest miR-155, miR-146a, and miR-21, among others, have been shown to have a number of specialized roles in the inflammatory process, Toll-like receptor signaling, and efferocytosis. Other important miRNAs that regulate inflammation are also discussed.
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References
Ferrero-Miliani L, Nielsen OH, Andersen PS, Girardin SE (2007) Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation. Clin Exp Immunol 147:227–235
Celsus (1935) De medicina. Heinemann, London
Roy S (2010) Resolution of inflammation in wound healing: significance of dead cell clearance. Mary Ann Liebert, New Rochelle, NY
Tedgui A (2011) Focus on inflammation. Arterioscler Thromb Vasc Biol 31:958–959
Nathan C (2002) Points of control in inflammation. Nature 420:846–852
Abbas AB, Lichtman AH (2009) Innate immunity. In: Abbas AB, Lichtman AH (eds) Basic immunology, functions and disorders of the immune system, Chap. 2, vol 3. Elsevier Saunders, Philadelphia
http://courses.washington.edu/hubio520/inflammation/Prelab/inflammation.html
Roy S, Sen CK (2012) miRNA in wound inflammation and angiogenesis. Microcirculation 19:224–232
Martin P (1997) Wound healing—aiming for perfect skin regeneration. Science 276:75–81
Menke NB, Ward KR, Witten TM, Bonchev DG, Diegelmann RF (2007) Impaired wound healing. Clin Dermatol 25:19–25
Shilo S, Roy S, Khanna S, Sen CK (2007) MicroRNA in cutaneous wound healing: a new paradigm. DNA Cell Biol 26:227–237
Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746
Broughton G 2nd, Janis JE, Attinger CE (2006) Wound healing: an overview. Plast Reconstr Surg 117:1e-S–32e-S
Roy S, Khanna S, Nallu K, Hunt TK, Sen CK (2006) Dermal wound healing is subject to redox control. Mol Ther 13:211–220
Gronert K (2008) Lipid autacoids in inflammation and injury responses: a matter of privilege. Mol Interv 8:28–35
Tonnesen MG, Feng X, Clark RA (2000) Angiogenesis in wound healing. J Investig Dermatol Symp Proc 5:40–46
Roy S, Das A (2012) In: Roy S, Bagchi D, Raychaudhuri SP (eds) Resolution of inflammation in chronic inflammation: molecular pathophysiology, nutritional and therapeutic interventions. CRC, Boca Raton, FL, pp 119–128
Eming SA, Krieg T, Davidson JM (2007) Inflammation in wound repair: molecular and cellular mechanisms. J Invest Dermatol 127:514–525
Dovi JV, Szpaderska AM, DiPietro LA (2004) Neutrophil function in the healing wound: adding insult to injury? Thromb Haemost 92:275–280
Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376
Roy S (2010) Resolution of wound inflammation: significance of apoptotic cell phagocytosis. In: Sen KD (ed) Advances in wound care, vol 2. Mary Ann Liebert, New Rochelle, NY, pp 76–81
Rajan VM, Murray RZ (2008) The duplicitous nature of inflammation in wound repair. Wound Pract Res 16:122–129
Ganesh K, Das A, Dickerson R, Khanna S, Parinandi NL, Gordillo GM, Sen CK, Roy S (2012) Prostaglandin E(2) induces oncostatin M expression in human chronic wound macrophages through Axl receptor tyrosine kinase pathway. J Immunol 189:2563–2573
http://www.worldwidewounds.com/2005/august/Schultz/Extrace-Matric-Acute-Chronic-Wounds.html
Das A, Ganesh K, Khanna S, Sen CK, Roy S (2014) Engulfment of apoptotic cells by macrophages: a role of microRNA-21 in the resolution of wound inflammation. J Immunol 192:1120–1129
deCathelineau AM, Henson PM (2003) The final step in programmed cell death: phagocytes carry apoptotic cells to the grave. Essays Biochem 39:105–117
Gardai SJ, Bratton DL, Ogden CA, Henson PM (2006) Recognition ligands on apoptotic cells: a perspective. J Leukoc Biol 79:896–903
Vandivier RW, Henson PM, Douglas IS (2006) Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 129:1673–1682
Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, Bhasker V, Gordillo GM, Sen CK, Roy S (2010) Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One 5:e9539
Tibrewal N, Wu Y, D’Mello V, Akakura R, George TC, Varnum B, Birge RB (2008) Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation. J Biol Chem 283:3618–3627
Martinez FO, Helming L, Gordon S (2009) Alternative activation of macrophages: an immunologic functional perspective. Annu Rev Immunol 27:451–483
Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G (2005) Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol 142:481–489
Martin P, Leibovich SJ (2005) Inflammatory cells during wound repair: the good, the bad and the ugly. Trends Cell Biol 15:599–607
Almeida JS, Benvegnu DM, Boufleur N, Reckziegel P, Barcelos RC, Coradini K, de Carvalho LM, Burger ME, Beck RC (2012) Hydrogels containing rutin intended for cutaneous administration: efficacy in wound healing in rats. Drug Dev Ind Pharm 38:792–799
Sonkoly E, Pivarcsi A (2009) Advances in microRNAs: implications for immunity and inflammatory diseases. J Cell Mol Med 13:24–38
Raisch J, Darfeuille-Michaud A, Nguyen HT (2013) Role of microRNAs in the immune system, inflammation and cancer. World J Gastroenterol 19:2985–2996
Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234
Gurtan AM, Sharp PA (2013) The role of miRNAs in regulating gene expression networks. J Mol Biol 425:3582–3600
Penn JW, Grobbelaar AO, Rolfe KJ (2012) The role of the TGF-beta family in wound healing, burns and scarring: a review. Int J Burns Trauma 2:18–28
Roy S, Sen CK (2011) MiRNA in innate immune responses: novel players in wound inflammation. Physiol Genomics 43:557–565
Graff JW, Dickson AM, Clay G, McCaffrey AP, Wilson ME (2012) Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem 287:21816–21825
Sabroe I, Parker LC, Dower SK, Whyte MK (2008) The role of TLR activation in inflammation. J Pathol 214:126–135
Takeda K, Akira S (2004) TLR signaling pathways. Semin Immunol 16:3–9
Rovin BH, Dickerson JA, Tan LC, Hebert CA (1995) Activation of nuclear factor-kappa B correlates with MCP-1 expression by human mesangial cells. Kidney Int 48:1263–1271
Viedt C, Dechend R, Fei J, Hansch GM, Kreuzer J, Orth SR (2002) MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-kappaB and activating protein-1. J Am Soc Nephrol 13:1534–1547
Chensue SW, Warmington KS, Ruth JH, Sanghi PS, Lincoln P, Kunkel SL (1996) Role of monocyte chemoattractant protein-1 (MCP-1) in Th1 (mycobacterial) and Th2 (schistosomal) antigen-induced granuloma formation: relationship to local inflammation, Th cell expression, and IL-12 production. J Immunol 157:4602–4608
van Zoelen MA, Verstege MI, Draing C, de Beer R, van’t Veer C, Florquin S, Bresser P, van der Zee JS, te Velde AA, von Aulock S, van der Poll T (2011) Endogenous MCP-1 promotes lung inflammation induced by LPS and LTA. Mol Immunol 48:1468–1476
Morris MC, Gilliam EA, Button J, Li L (2014) Dynamic modulation of innate immune response by varying dosages of lipopolysaccharide (LPS) in human monocytic cells. J Biol Chem 289:21584–21590
Tili E, Croce CM, Michaille JJ (2009) miR-155: on the crosstalk between inflammation and cancer. Int Rev Immunol 28:264–284
Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899
Wu T, Xie M, Wang X, Jiang X, Li J, Huang H (2012) miR-155 modulates TNF-alpha-inhibited osteogenic differentiation by targeting SOCS1 expression. Bone 51:498–505
Faraoni I, Antonetti FR, Cardone J, Bonmassar E (2009) miR-155 gene: a typical multifunctional microRNA. Biochim Biophys Acta 1792:497–505
Lindsay MA (2008) microRNAs and the immune response. Trends Immunol 29:343–351
Trotta R, Chen L, Costinean S, Josyula S, Mundy-Bosse BL, Ciarlariello D, Mao C, Briercheck EL, McConnell KK, Mishra A, Yu L, Croce CM, Caligiuri MA (2013) Overexpression of miR-155 causes expansion, arrest in terminal differentiation and functional activation of mouse natural killer cells. Blood 121:3126–3134
Du F, Yu F, Wang Y, Hui Y, Carnevale K, Fu M, Lu H, Fan D (2014) MicroRNA-155 deficiency results in decreased macrophage inflammation and attenuated atherogenesis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 34:759–767
Babar IA, Cheng CJ, Booth CJ, Liang X, Weidhaas JB, Saltzman WM, Slack FJ (2012) Nanoparticle-based therapy in an in vivo microRNA-155 (miR-155)-dependent mouse model of lymphoma. Proc Natl Acad Sci U S A 109:E1695–E1704
Ma X, Ma C, Zheng X (2013) MicroRNA-155 in the pathogenesis of atherosclerosis: a conflicting role? Heart Lung Circ 22:811–818
Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y, Zhang J, Zhang J, Fu X, Liu H, Lu L, Wu Y (2010) Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther 12:R81
Xu N, Zhang L, Meisgen F, Harada M, Heilborn J, Homey B, Grander D, Stahle M, Sonkoly E, Pivarcsi A (2012) MicroRNA-125b down-regulates matrix metallopeptidase 13 and inhibits cutaneous squamous cell carcinoma cell proliferation, migration, and invasion. J Biol Chem 287:29899–29908
Rusca N, Monticelli S (2011) MiR-146a in immunity and disease. Mol Biol Int 2011:437301
Boldin MP, Taganov KD, Rao DS, Yang L, Zhao JL, Kalwani M, Garcia-Flores Y, Luong M, Devrekanli A, Xu J, Sun G, Tay J, Linsley PS, Baltimore D (2011) miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med 208:1189–1201
Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J (2009) MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8. Aging (Albany NY) 1:402–411
Sen CK, Roy S (2012) MicroRNA 21 in tissue injury and inflammation. Cardiovasc Res 96:230–233
Lu TX, Munitz A, Rothenberg ME (2009) MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression. J Immunol 182:4994–5002
Kumarswamy R, Volkmann I, Thum T (2011) Regulation and function of miRNA-21 in health and disease. RNA Biol 8:706–713
Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K (2010) STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell 39:493–506
Sicard F, Gayral M, Lulka H, Buscail L, Cordelier P (2013) Targeting miR-21 for the therapy of pancreatic cancer. Mol Ther 21:986–994
Roy SG, De P (2014) pH responsive polymers with amino acids in the side chains and their potential applications. J Appl Polym Sci 131:41084
Kooistra SM, Norgaard LC, Lees MJ, Steinhauer C, Johansen JV, Helin K (2014) A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence. PLoS One 9:e91034
Sun X, He S, Wara AK, Icli B, Shvartz E, Tesmenitsky Y, Belkin N, Li D, Blackwell TS, Sukhova GK, Croce K, Feinberg MW (2014) Systemic delivery of microRNA-181b inhibits nuclear factor-kappaB activation, vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice. Circ Res 114:32–40
Sun X, Icli B, Wara AK, Belkin N, He S, Kobzik L, Hunninghake GM, Vera MP, Registry M, Blackwell TS, Baron RM, Feinberg MW (2012) MicroRNA-181b regulates NF-kappaB-mediated vascular inflammation. J Clin Invest 122:1973–1990
Wang S, Liu Z, Wang L, Zhang X (2009) NF-kappaB signaling pathway, inflammation and colorectal cancer. Cell Mol Immunol 6:327–334
Xie W, Li M, Xu N, Lv Q, Huang N, He J, Zhang Y (2013) MiR-181a regulates inflammation responses in monocytes and macrophages. PLoS One 8:e58639
Sun YM, Lin KY, Chen YQ (2013) Diverse functions of miR-125 family in different cell contexts. J Hematol Oncol 6:6
Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM (2007) Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol 179:5082–5089
Kim SW, Ramasamy K, Bouamar H, Lin AP, Jiang D, Aguiar RC (2012) MicroRNAs miR-125a and miR-125b constitutively activate the NF-kappaB pathway by targeting the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20). Proc Natl Acad Sci U S A 109:7865–7870
Chaudhuri AA, So AY, Sinha N, Gibson WS, Taganov KD, O’Connell RM, Baltimore D (2011) MicroRNA-125b potentiates macrophage activation. J Immunol 187:5062–5068
Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86
Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, Brummelkamp TR, Fleming MD, Camargo FD (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451:1125–1129
Baltimore D, Boldin MP, O’Connell RM, Rao DS, Taganov KD (2008) MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9:839–845
Xiao C, Srinivasan L, Calado DP, Patterson HC, Zhang B, Wang J, Henderson JM, Kutok JL, Rajewsky K (2008) Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92 expression in lymphocytes. Nat Immunol 9:405–414
Lanford RE, Hildebrandt-Eriksen ES, Petri A, Persson R, Lindow M, Munk ME, Kauppinen S, Orum H (2010) Therapeutic silencing of microRNA-122 in primates with chronic hepatitis C virus infection. Science 327:198–201
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17:211–215
Obad S, dos Santos CO, Petri A, Heidenblad M, Broom O, Ruse C, Fu C, Lindow M, Stenvang J, Straarup EM, Hansen HF, Koch T, Pappin D, Hannon GJ, Kauppinen S (2011) Silencing of microRNA families by seed-targeting tiny LNAs. Nat Genet 43:371–378
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Supported by NIH grant GM077185, GM069589, NR013898 to CKS and NIH DK076566 to SR.
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Das, A., Chaffee, S., Sen, C.K., Roy, S. (2015). Wound Inflammation: Emerging Role of miRNA. In: Greene, C. (eds) MicroRNAs and Other Non-Coding RNAs in Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-13689-9_7
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DOI: https://doi.org/10.1007/978-3-319-13689-9_7
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