Transcriptional profiling of rapamycin-treated fibroblasts from hypertrophic and keloid scars

Annals of Plastic Surgery

Volumn 72, Issue SUPPL. 2, 2014, Pages 711-719

  Wong, Victor W ^a,b   You, Fanglei ^a   Januszyk, Michael ^b   Gurtner, Geoffrey C ^b   Kuang, Anna A ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b STANFORD UNIVERSITY   (United States)

Author keywords

Collagen; Fibroblast; Hypertrophic scar; Keloid; Microarray

Indexed keywords

COLLAGEN; IMMUNOSUPPRESSIVE AGENT; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

ADULT; AGED; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; CICATRIX, HYPERTROPHIC; DOSE RESPONSE; DOWN REGULATION; DRUG EFFECTS; FEMALE; FIBROBLAST; HUMAN; KELOID; MALE; METABOLISM; MIDDLE AGED; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN MICROARRAY;

ADULT; AGED; CICATRIX, HYPERTROPHIC; COLLAGEN; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; FEMALE; FIBROBLASTS; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KELOID; MALE; MIDDLE AGED; PHOSPHORYLATION; PROTEIN ARRAY ANALYSIS; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84901334429     PISSN: 01487043     EISSN: 15363708     Source Type: Journal    
DOI: 10.1097/SAP.0b013e31826956f6     Document Type: Article

References (53)

1. Kose O,Waseem A. Keloids and hypertrophic scars: are they two different sides of the same coin? Derm Surg. 2008;34: 336-346.
2. Ogawa R. Keloid and hypertrophic scarring may result from a mechanoreceptor or mechanosensitive nociceptor disorder. Med Hypotheses. 2008;71: 493-500.
3. Lee JYY, Yang CC, Chao SC, et al. Histopathological differential diagnosis of keloid and hypertrophic scar. Amer J Dermatopathol. 2004;26: 379-384.
4. Teofoli P, Barduagni S, Ribuffo M, et al. Keloids and hypertrophic scars: study of apoptotic regulatory genes with evidence of possible altered cell death pathway. J Derm Sci. 1998;16:S128.
5. Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110: 560-571.
6. Gauglitz GG, Korting HC, Pavicic T, et al. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med. 2011;17: 113-125.
7. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg. 2008;206: 731-741.
8. Ueda K, Furuya E, Yasuda Y, et al. Keloids have continuous high metabolic activity. Plast Reconstr Surg. 1999;104: 694-698.
9. Dennis PB, Jaeschke A, Saitoh M, et al. Mammalian TOR: a homeostatic ATP sensor. Science. 2001;294: 1102-1105.
10. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004; 18: 1926-1945.
11. Ong CT, Khoo YT, Mukhopadhyay A, et al. mTOR as a potential therapeutic target for treatment of keloids and excessive scars. Exp Dermatol. 2007;16: 394-404.
12. Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol. 2005;17: 596-603.
13. Shegogue D, Trojanowska M. Mammalian target of rapamycin positively regulates collagen type I production via a phosphatidylinositol 3-kinase-independent pathway. J Biol Chem. 2004;279: 23166-23175.
14. Wong VW, Rustad KC, Akaishi S, et al. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat Med. 2012;18: 148-152.
15. Ala-Kokko L, Rintala A, Savolainen ER. Collagen gene expression in keloids: analysis of collagen metabolism and type I, III, IV, and V procollagen mRNAs in keloid tissue and keloid fibroblast cultures. J Invest Dermatol. 1987;89: 238-244.
16. Friedman DW, Boyd CD, Mackenzie JW, et al. Regulation of collagen gene expression in keloids and hypertrophic scars. J Surg Res. 1993;55: 214-222.
17. Oliveira GV, Hawkins HK, Chinkes D, et al. Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: type I and III collagens. Int Wound J. 2009;6: 445-452.
18. Wu J, Ma B, Yi S, et al. Gene expression of early hypertrophic scar tissue screened by means of cDNA microarrays. J Trauma. 2004;57: 1276-1286.
19. Paddock HN, Schultz GS, Baker HV, et al. Analysis of gene expression patterns in human postburn hypertrophic scars. J Burn Care Rehabil. 2003;24: 371-377.
20. Tsou R, Cole JK, Nathens AB, et al. Analysis of hypertrophic and normal scar gene expression with cDNA microarrays. J Burn Care Rehabil. 2000;21: 541-550.
21. Engrav LH, Tuggle CK, Kerr KF, et al. Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring. PloS one. 2011;6:e19024.
22. Wong VW, Paterno J, Sorkin M, et al. Mechanical force prolongs acute inflammation via T-cell-dependent pathways during scar formation. FASEB J. 2011;25: 4498-4510.
23. Dasu MR, Hawkins HK, Barrow RE, et al. Gene expression profiles from hypertrophic scar fibroblasts before and after IL-6 stimulation. J Pathol. 2004; 202: 476-485.
24. ChenW, Fu X, Sun X, et al. Analysis of differentially expressed genes in keloids and normal skin with cDNA microarray. J Surg Res. 2003;113: 208-216.
25. Nassiri M,Woolery-Lloyd H, Ramos S, et al. Gene expression profiling reveals alteration of caspase 6 and 14 transcripts in normal skin of keloid-prone patients. Arch Dermatol Res. 2009;301: 183-188.
26. Smith JC, Boone BE, Opalenik SR, et al. Gene profiling of keloid fibroblasts shows altered expression in multiple fibrosis-associated pathways. J Invest Dermatol. 2008;128: 1298-1310.
27. Russell SB, Russell JD, Trupin KM, et al. Epigenetically altered wound healing in keloid fibroblasts. J Invest Dermatol. 2010;130: 2489-2496.
28. Tosa M, Ghazizadeh M, Shimizu H, et al. Global gene expression analysis of keloid fibroblasts in response to electron beam irradiation reveals the involvement of interleukin-6 pathway. J Invest Dermatol. 2005;124: 704-713.
29. Shih B, McGrouther DA, Bayat A. Identification of novel keloid biomarkers through profiling of tissue biopsies versus cell cultures in keloid margin specimens compared to adjacent normal skin. Eplasty. 2010;10:e24.
30. Meyer LJ, Russell SB, Russell JD, et al. Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts. J Invest Dermatol. 2000;114: 953-959.
31. De Felice B, Garbi C, Santoriello M, et al. Differential apoptosis markers in human keloids and hypertrophic scars fibroblasts. Mol Cell Biochem. 2009;327: 191-201.
32. Poulalhon N, Farge D, Roos N, et al. Modulation of collagen and MMP-1 gene expression in fibroblasts by the immunosuppressive drug rapamycin. A direct role as an antifibrotic agent? J Biol Chem. 2006;281: 33045-33052.
33. Chen G, Chen H, Wang C, et al. Rapamycin ameliorates kidney fibrosis by inhibiting the activation of mTOR signaling in interstitial macrophages and myofibroblasts. PloS ONE. 2012;7:e33626.
34. Goc A, Choudhary M, Byzova TV, et al. TGFbeta- and bleomycin-induced extracellular matrix synthesis is mediated through Akt and mammalian target of rapamycin (mTOR). J Cell Physiol. 2011;226: 3004-3013.
35. Yoshizaki A, Yanaba K, Iwata Y, et al. Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis. Arthritis Rheum. 2010;62: 2476-2487.
36. Gragnani A, Warde M, Furtado F, et al. Topical tamoxifen therapy in hypertrophic scars or keloids in burns. Arch Dermatol Res. 2010;302: 1-4.
37. Wu WS, Wang FS, Yang KD, et al. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol. 2006;126: 1264-1271.
38. Mogili NS, Krishnaswamy VR, Jayaraman M, et al. Altered angiogenic balance in keloids: a key to therapeutic intervention. Transl Res. 2012;159: 182-189.
39. Salem A, Assaf M, Helmy A, et al. Role of vascular endothelial growth factor in keloids: a clinicopathologic study. Int J Dermatol. 2009;48: 1071-1077.
40. van der Slot AJ, Zuurmond AM, Bardoel AF, et al. Identification of PLOD2 as telopeptide lysyl hydroxylase, an important enzyme in fibrosis. J Biol Chem. 2003;278: 40967-40972.
41. Renzoni EA, Abraham DJ, Howat S, et al. Gene expression profiling reveals novel TGFbeta targets in adult lung fibroblasts. Respir Res. 2004;5: 24.
42. van der Slot AJ, Zuurmond AM, van den Bogaerdt AJ, et al. Increased formation of pyridinoline cross-links due to higher telopeptide lysyl hydroxylase levels is a general fibrotic phenomenon. Matrix Biol. 2004;23: 251-257.
43. Newman AC, Nakatsu MN, Chou W, et al. The requirement for fibroblasts in angiogenesis: fibroblast-derived matrix proteins are essential for endothelial cell lumen formation. Mol Biol Cell. 2011;22: 3791-3800.
44. Steiglitz BM, Kreider JM, Frankenburg EP, et al. Procollagen C proteinase enhancer 1 genes are important determinants of the mechanical properties and geometry of bone and the ultrastructure of connective tissues. Mol Cell Biol. 2006;26: 238-249.
45. Achari Y, Chin JW, Heard BJ, et al. Molecular events surrounding collagen fibril assembly in the early healing rabbit medial collateral ligamentVfailure to recapitulate normal ligament development. Connect Tissue Res. 2011;52: 301-312.
46. Kessler-Icekson G, Schlesinger H, Freimann S, et al. Expression of procollagen C-proteinase enhancer-1 in the remodeling rat heart is stimulated by aldosterone. Int J Biochem Cell Biol. 2006;38: 358-365.
47. Matsui A, Yanase M, Tomiya T, et al. Stabilization of RNA strands in protein synthesis by type I procollagen C-proteinase enhancer protein, a potential RNAbinding protein, in hepatic stellate cells. Biochem Biophys Res Commun. 2002;290: 898-902.
48. Bekhouche M, Kronenberg D, Vadon-Le Goff S, et al. Role of the netrin-like domain of procollagen C-proteinase enhancer-1 in the control of metalloproteinase activity. J Biol Chem. 2010;285: 15950-15959.
49. Myllyharju J. Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets. Ann Med. 2008;40: 402-417.
50. Kim I, Mogford JE,Witschi C, et al. Inhibition of prolyl 4-hydroxylase reduces scar hypertrophy in a rabbit model of cutaneous scarring. Wound Repair Regen. 2003;11: 368-372.
51. McCoy BJ, Diegelmann RF, Cohen IK. In vitro inhibition of cell growth, collagen synthesis, and prolyl hydroxylase activity by triamcinolone acetonide. Proc Soc Exp Biol Med. 1980;163: 216-222.
52. Beyer C, Schramm A, Akhmetshina A, et al. beta-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis. Ann Rheum Dis. 2012;71: 761-767.
53. Arwert EN, Hoste E,Watt FM. Epithelial stem cells, wound healing and cancer. Nat Rev Cancer. 2012;12: 170-180.