MicroRNA in keloid pathogenesis

Hajime Shimizu, Ramin Ghazizadeh, Mohammad Ghazizadeh


Keloid is a fibro-proliferative lesion that develops as a result of abnormal wound healing in susceptible individuals. Many factors such as skin tension, wound infection, racial difference and genetic predisposition have been implicated in the etiology of keloid. MicroRNAs are highly conserved noncoding small RNA sequences and are key posttranscriptional gene regulators that contribute to the maintenance of differentiated cell phenotype. In this review, we outline the results of the studies on the expression of various miroRNAs in keloid as well as their role in pathogenesis of this lesion.


MicroRNA, keloid fibroblast, normal dermal fibroblast, mechanism, pathogenesis, type Ⅰ procollagen

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Ma S, Chang WP, Fang RH. Measurement of radiation-induced DNA double-strand breaks in human diploid fibroblasts from keloid and normal skin by single-cell gel electrophoresis. Plast Reconstr Surg 5:821-826, 1996.

Syed F, Ahmadi E, Iqbal SA, Singh S, McGrouther DA, Bayat A. Fibroblasts from the growing margin of keloid scars produce higher levels of collagen I and III compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy. Br J Dermatol 164:83-96, 2011.

Berman B, Bleley HC. Adjunct therapies to surgical management of keloids. Durmatol Surg 2282:126-130, 1996.

Ragoowansi R, Cormer PG, Moss AL, Gless JP. Treatment of keloids by surgical excision and immediate postoperative single-fraction radiotherapy. Plast Reconstr Surg 111:1853-1859, 2003.

Tosa M, Ghazizadeh M, Shimizu H, Hirai T, Hyakusoku H, Kawanami O. Global gene expression analysis of keloid fibroblasts in response to electron beam irradiation reveals the involvement of interleukin-6 pathway. J Invest Dermatol 124:704-713, 2005.

Ghazizadeh M, Tosa M, Shimizu H, Kawanami O. Functional implications of the IL-6 signaling pathway in keloid pathogenesis. J Invest Dermatol 127:98-105, 2006.

Ambrous V. The functions of animal microRNAs. Nature 16,431: 350-355, 2004.

Bartel DP. MicroNAs: Target recognition and

regulatory functions. Cell 136:215-233, 2009.

Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9: 102-114, 2008.

Van Rooiji E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Maeshall WS, Hill JA, Oison EN. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. PNAS 105: 13027-13032, 2008.

Jiang X, Tsitsiou E, Herrick SE, Lindsay MA. MicroRNAs and the regulation of fibrosis. FEBS J 277: 2015-2021, 2010.

Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JH, Gay S, Distler O. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum 62(6):1733-1743, 2010.

Rodenburg C, Urban GW, Bettermann K, Vucur M, Zimmermann H, Schmidt S, Janssen J, Koppe C, Knolle P, Castoldi M, Tacke F, Trautwein C, Luedde T. Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology 53:209-218, 2011.

Thum T, Gross C, Fiedler J, Fischer T, Kissler S. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signaling in fibroblasts. Nature 18,456:980-984, 2008.

Liu G, Friggeri A, Yang Y, Milosevic J, Ding Q, Thannickal VJ, Kaminski N, Abraham E. miR-21 mediates fibrogenic activation of pulmonary fibroblasts and lung fibrosis. J Exp Med 207:1589-1597, 2010.

Thum T, Chau N, Bhat B, Gupta SK, Linsley PS, Bauersachs J, Engelhardt S. Comparison of different miR-21 inhibitor chemistries in a cardiac disease model. J Clin Invest 121:461-462, 2011.

Ghazizadeh M. (2007) Essential role of IL-6 signaling pathway in keloid pathogenesis. J Nippon Med Sch 74:11-22, 2007.

Liu Y, Yang D, Xiao Z, Zhang M. miRNA expression profiles in keloid tissue and corresponding normal skin tissue. Aesthetic Plast Surg 36:193-201, 2012.

Kashiyama K, Mitsutake N, Matsuse M, Ogi T, Saenco VA, Ujifuku K, Utani A, Hirano A, Yamashita S. (2012) miR-196a downregulation increases the expression of type I and III collagens in keloid fibroblasts. J Invest Dermatol 132:1597-1604, 2012.

Phillippe L, Alsaleh G, Suffert G, Meyer A, Georgel P, Sibilla J, Wachsmann D, Pfeffer S. TLR2 expression is regulated by microRNA miR-19 in rheumatoid fibroblast-like synoviocytes. J Immunol 188:454-461, 2012.

Chau BN, Brenner DA.What goes up must come down: the emerging role of microRNA in fibrosis. Hepatology 53:4-6, 2011.

Zhu H, Li Y, Qu S, Luo H, Zhou Y, Wang W, Zhao H, You Y, Xiao X, Zuo X. MicroRNA expression abnormalities in limited cutaneous scleroderma and diffuse cutaneous scleroderma. J Clin Immunol 32(3): 514-22, 2012.

Ørom UA, Nielsen FC, Lund AH. MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell 30:460-471, 2008.

Agirre X, Jiménez-Velasco A, San José-Enériz E, et al. Down-regulation of hsa-miR-10a in chronic myeloid leukemia CD34+ cells increases USF2-mediated cell growth. Mol Cancer Res 6:1830-1840, 2008.

Garzon R, Pichiorri F, Palumbo T, Luliano R, Cimmino A, Aqeilan R, Volinia S, Bhatt D, Alder H, Marcucci G, Calin GA, Liu CG, Bloomfield CD, Andreeff M, Croce CM. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci 103: 5078-5083, 2006.

Fang Y, Shi C, Manduchi E, Civelek M, Davies PF. MicroRNA-10a regulation of proinflammatory phenotype in athero-susceptible endothelium in vivo and in vitro. Proc Natl Acad Sci 107:13450-13455, 2010.

Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449:682-688, 2007.

Zhang X, Zhu T, Chen Y, Mertani HC, Lee KO, Lobie PE. Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. J Biol Chem 278:7580-7590, 2003.

Lee NS, Kim JS, Cho WJ, Lee MR, Steiner R, Gompers A, Ling D, Zhang J, Strom P, Behlke M, Moon SH, Salvaterra PM, Jove R, Kim KS. MiR-302b maintains "stemness" of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression. Biochem Biophys Res Commun 377:434-440, 2008.

Huang H, Xie C, Sun X, Ritchie RP, Zhang J, Chen YE. MiR-10a contributes to retinoid acid-induced smooth muscle cell differentiation. J Biol Chem 285: 9383-9389, 2010.

Weiss FU, Marques IJ, Woltering JM, Vlecken DH, Aghdassi A, Parteckle LI, Heidecke CD, Lerch MM, Bagowski CP. Retinoic acid receptor antagonists inhibit miR-10a expression and block metastatic behavior of pancreatic cancer. Gastroenterogy 137:2136-2145, 2009.

Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications. Nat Rev Genet 10: 578-585, 2009.

Bak RO, Mikkelsen JG. Regulation of cytokines by small RNAs during skin inflammation. J Biomed Sci 17:53,

Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, Stoffel M. Silencing of microRNAs in vivo with 'antagomirs'. Nature 438:685-689, 2005.

Scherr M, Venturini L, Battmer K, Schaller Schoenitz M, Schaefer D, Dallmann I, Ganser A, Eder M. Lentivirus-mediated antagomir expression for specific inhibition of miRNAfunction. Nucleic Acids Res 35:e149, 2007.

Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson E, Teruya-Feldstein J, Bell GW, Weinberg RA. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28:341-347, 2010.


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