Как собрать компьютер самостоятельно. Быстро собираем компьютер сами. Как правильно собрать компьютер. Восстановить удаленные файлы с флешки. Как восстановить флешку transcend. Восстановить флешку бесплатно. Учим язык java онлайн. Java для начинающих уроки. Все о программах java. Google nexus 7 обзор. Лучший планшет nexus 7 обзор. Google nexus 7 обзор планшета. Интересные картинки со смыслом. Самые интересные картинки скачать. Фото картинки интересные. Wow шп прист. Лучший гайд по присту wow. Прист wow билд. Учим язык python с самого нуля. python для начинающих уроки. Все о языке python 3. Расширения для Joomla. Скачать последние расширения для joomla. Скачать бесплатно все расширения joomla.

MicroRNA-203 contributes to skin re-epithelialization

G Viticchie, AM Lena, F Cianfarani, T Odorisio, M Annicchiarico-Petruzzelli, G Melino and E Candi


Cell Death and Disease (2012) 3, e435


Читать статью


Keratinocyte proliferation and migration are crucial steps for the rapid closure of the epidermis during wound healing, but the molecular mechanisms involved in this cellular response remain to be completely elucidated. Here, by in situ hybridization we characterize the expression pattern of miR-203 after the induction of wound in mouse epidermis, showing that its expression is downregulated in the highly proliferating keratinocytes of the ‘migrating tongue’, whereas it is strongly expressed in the differentiating cells of the skin outside the wound. Furthermore, subcutaneous injections of antagomiR-203 in new born mice dorsal skin strengthened, in vivo, the inverse correlation between miR-203 expression and two new target mRNAs: RAN and RAPH1. Our data suggest that miR-203, by controlling the expression of target proteins that are responsible for both keratinocyte proliferation and migration, exerts a specific role in wound re-epithelialization and epidermal homeostasis re-establishment of injured skin.


1. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341: 738–746.

2. Grinnel F. Wound repair, keratinocyte activation and integrin modulation. J Cell Sci 1992; 101: 1–5.

3. Coulombe PA. Towards a molecular definition of keratinocyte activation after acute injury to stratified epithelia. Biochem Biophys Res Commun 1997; 236: 231–238.

4. Freedberg IM, Tomic-Canic M, Komine M, Blumenberg M. Keratins and the keratinocyte activation cycle. J Invest Dermatol 2001; 116: 633–640.

5. Santoro MM, Gaudino G. Cellular and molecular facets of keratinocytes reepithelialization during wound healing. Exp Cell Res 2005; 31: 674–686.

6. Proksch E, Brandner JM, Jensen JM. The skin: an indispensable barrier. Exp Dermatol 2008; 17: 1063–1072.

7. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 2005; 6: 328–340.

8. Patel GK, Wilson CH, Harding KG, Finlay AY, Bowden PE. Numerous keratinocytes subtypes involved in wound re-epithelialization. J Invest Dermatol 2006; 126: 497–502.

9. Levy V, Lindon C, Harfe BD, Morgan BA. Distinct stem cell populations regenerate the follicle and interfollicular epidermis. Dev Cell 2005; 9: 855–861.

10. Langton AK, Herrick SE, Headon DJ. An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol 2008; 128: 1311–1318.

11. Paladini RD, Takahashi K, Bravo NS, Coulombe PA. Onset of re-epithelialization after skin injury correlates with reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J Cell Biol 1996; 236: 231–238.

12. DePianto D, Coulombe PA. Intermediate filaments and tissue repair. Exp Cell Res 2004; 301: 68–76.

13. Tomic-Canic M, Komine M, Freedberg IM, Blumenberg M. Epidermal signal transduction and transcription factors activation in activated keratinocytes. J Dermatol Sci 1998; 17: 167–181.

14. Scha¨ fer M, Werner S. Transcriptional control of wound repair. Ann Rev Cell Dev Biol 2007; 23: 69–72.

15. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 2008; 453: 314–321.

16. Banerjee J, Chan YC, Sen CK. MicroRNAs in skin and wound healing. Physiol Genomics 2011; 43: 543–556.

17. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism and function. Cell 2004; 116: 281–297.

18. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 2010; 11: 597–610.

19. Aberdam D, Candi E, Knight RA, Melino G. miRNAs, ’stemness’ and skin. Trends Biochem Sci 2008; 33: 583–591.

20. Sand M, Gambichler T, Sand D, Skrygan M, Altmeyer P, Bechara FG. MicroRNAs and the skin: tiny players in the body’s largest organ. J Dermatol Sci 2009; 53: 169–175.

21. Yi R, Fuchs E. MicroRNA-mediated control in the skin. Cell Death Differ 2010; 17: 229–235.

22. Lena AM, Shalom-Feuerstein R, Rivetti di Val Cervo P, Aberdam D, Knight RA, Melino G et al. miR-203 represses ‘stemness’ by repressing DeltaNp63. Cell Death Differ 2008; 15: 1187–1195.

23. Lena AM, Mancini M, Rivetti di Val Cervo P, Saintigny G, Mahe´ C, Melino G et al. MicroRNA-191 triggers keratinocytes senescence by SATB1 and CDK6 downregulation. Biochem Biophys Res Commun 2012; 423: 509–514.

24. Rivetti di Val Cervo P, Lena AM, Nicoloso M, Rossi S, Mancini M, Zhou H et al. P63- microRNA feedback in keratinocyte senescence. Proc Natl Acad Sci USA 2012; 109: 1133–1138.

25. Sonkoly E, Wei T, Janson PC, Sa¨a¨ f A, Lundeberg L, Tengvall-Linder M et al. MicroRNAs: novel regulators involved in the pathogenesis of psoriasis? PLoS One 2007; 2: e610.

26. Yi R, Poy MN, Stoffel M, Fuchs E. A skin microRNA promotes differentiation by repressing ‘stemness’. Nature 2008; 452: 225–229.

27. Senoo M, Pinto F, Crum CP, McKeon F. P63 Is essential for the proliferative potential of stem cells in stratified epithelia. Cell 2007; 129: 523–536.

28. Masse I, Barbollat-Boutrand L, Molina M, Berthier-Vergnes O, Joly-Tonetti N, Martin MT et al. Functional interplay between p63 and p53 controls RUNX1 function in the transition from proliferation to differentiation in human keratinocytes. Cell Death Dis 2012; 3: e318.

29. Barton CE, Johnson KN, Mays DM, Boehnke K, Shyr Y, Boukamp P et al. Novel p63 target genes involved in paracrine signaling and keratinocyte differentiation. Cell Death Dis 2010; 1: e74.

30. Straub WE, Weber TA, Scha¨ fer B, Candi E, Durst F, Ou HD et al. The C-terminus of p63 contains multiple regulatory elements with different functions. Cell Death Dis 2010; 1: e5.

31. Borrelli S, Candi E, Hu B, Dolfini D, Ravo M, Grober OM et al. The p63 target HBP1 is required for skin differentiation and stratification. Cell Death Differ 2010; 17: 1896–1907.

32. Talos F, Wolff S, Beyer U, Dobbelstein M, Moll UM. Brdm2 – an aberrant hypomorphic p63 allele. Cell Death Differ 2010; 17: 184–186.

33. Lena AM, Cipollone R, Amelio I, Catani MV, Ramadan S, Browne G et al. Skn-1a/Oct-11 and DNp63a exert antagonizing effects on human keratin expression. Biochem Biophys Res Commun 2010; 401: 568–573.

34. Shalom-Feuerstein R, Lena AM, Zhou H, De La Forest Divonne S, Van Bokhoven H, Candi E et al. DNp63 is an ectodermal gatekeeper of epidermal morphogenesis. Cell Death Differ 2011; 18: 887–896.

35. Aberdam D, Mantovani R. A new p63-deficient mouse model or a fresh look at an old one? Cell Death Differ 2009; 16: 1073–1074.

36. Wolff S, Talos F, Palacios G, Beyer U, Dobbelstein M, Moll UM. The alpha/beta carboxyterminal domains of p63 are required for skin and limb development. New insights from the Brdm2 mouse which is not a complete p63 knockout but expresses p63 gamma-like proteins. Cell Death Differ 2009; 16: 1108–1117.

37. Vanbokhoven H, Melino G, Candi E, Declercq W. P63, a story of mice and men. J Invest Dermatol 2011; 131: 1196–1207.

38. Leonard MK, Kommagani R, Payal V, Mayo LD, Shamma HN, Kadakia MP. DNp63a regulates keratinocyte proliferation by controlling PTEN expression and localization. Cell Death Differ 2011; 18: 1924–1933.

39. Collavin L, Lunardi A, Del Sal G. P53-family proteins and their regulators: hubs and spokes in tumor suppression. Cell Death Differ 2010; 17: 901–911.

40. Browne G, Cipollone R, Lena AM, Serra V, Zhou H, van Bokhoven H et al. Differential altered stability and transcriptional activity of DNp63 mutants in distinct ectodermal dysplasias. J Cell Sci 2011; 124(Part 13): 2200–2207.

41. Melino G. P63 is a suppressor of tumorigenesis and metastasis interacting with mutant p53. Cell Death Differ 2011; 18: 1487–1499.

42. Bueno MJ, Pe´ rez de Castro I, Go´mez de Cedro´n M, Santos J, Calin GA, Cigudosa JC et al. Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 2008; 13: 496–506.

43. Feber A, Xi L, Luketich JD, Pennathur A, Landreneau RJ, Wu M et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg 2008; 135: 255–260.

44. Furuta M, Kozaki KI, Tanaka S, Arii S, Imoto I, Inazawa J. MiR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis 2010; 31: 766–776.

45. Saini S, Majid S, Yamamura S, Tabatabai L, Suh SO, Shahryari V et al. Regulatory role of miR-203 in prostate cancer progression and metastasis. Clin Cancer Res 2011; 17: 5287–5298.

46. Viticchie` G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle 2011; 10: 1121–1131.

47. Wellner U, Schubert J, Burk UC, Schmalhofer O, Zhu F, Sonntag A et al. The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol 2009; 11: 1487–1495.

48. Rensen WM, Mangiacasale R, Ciciarello M, Lavia P. The GTPase Ran: regulation of cell life and potential roles in cell transformation. Front Biosci 2008; 13: 4097–4121.

49. Yudin D, Fainzilber M. Ran on tracks-cytoplasmic roles for a nuclear regulator. J Cell Sci 2009; 122: 587–593.

50. Jeon H, Zheng LT, Lee S, Lee WH, Park N, Park JY et al. Comparative analysis of the role of small G proteins in cell migration and cell death: cytoprotective and promigratory effects of RalA. Exp Cell Res 2011; 317: 2007–2018.

51. Lafuente EM, van Puijenbroek A, Krause M, Carman CV, Freeman GJ, Berezovskaya A et al. RIAM, an Ena/VASP and Profilin ligand, interacts with Rap1-GTP and mediates Rap1-induced adhesion. Dev Cell 2004; 7: 585–595.

52. Bae YH, Ding Z, Das T, Wells A, Gertler F, Roy P. Profilin1 regulates PI(3,4)P2 and lamellipodin accumulation at the leading edge thus influencing motility of MDA-MB-231 cells. Proc Natl Acad Sci USA 2010; 107: 21547–21552.

53. Herna´ndez-Varas P, Colo´ GP, Bartolome´ RA, Paterson A, Medran˜o-Ferna´ndez I, Arellano-Sa´nchez N et al. Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells. J Biol Chem 2011; 286: 18492–18504.

54. Kru¨ tzfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M et al. Silencing of microRNAs in vivo with ‘antagomirs’. Nature 2005; 438: 685–689.

55. Shilo S, Roy S, Khanna S. MicroRNA in cutaneous wound healing: a new paradigm. DNA Cell Biol 2007; 26: 227–237.

56. Bamberger C, Hafner A, Schmale H, Werner S. Expression of different p63 variants in healing skin wounds suggests a role of p63 in reepithelialization and muscle repair. Wound Repair Regen 2005; 13: 41–50.

57. Koster MI, Dai D, Marinari B, Sano Y, Costanzo A, Karin M et al. P63 induces key target genes required for epidermal morphogenesis. Proc Natl Acad Sci USA 2007; 104: 3255–3260.

58. Yuspa SH, Kilkenny AE, Steinert PM, Roop DR. Expression of murine epidermal differentiation markers is tightly regulated by restricted extracellular calcium concentrations in vitro. J Cell Biol 1989; 109: 1207–1217.

59. Cianfarani F, Zambruno G, Brogelli L, Sera F, Lacal PM, Pesce M et al. Placenta growth factor in diabetic wound healing. Altered expression and therapeutic potential. Am J Pathol 2006; 169: 1167–1182.

60. Candi E, Rufini A, Terrinoni A, Giamboi-Miraglia A, Lena AM, Mantovani R et al. DeltaNp63 regulates thymic development through enhanced expression of FgfR2 and Jag2. Proc Natl Acad Sci USA 2007; 104: 11999–12004.

Прочитано 2462 раз
Оцените материал
(0 голосов)
Опубликовано в СТАТЬИ
Авторизуйтесь, чтобы получить возможность оставлять комментарии


Управление научных исследований СПбГТИ (ТУ)

Горячие новости

Приборное оснащение лаборатории

Rambler's Top100
//'+ 'Рейтинг@Mail.ru<\/a><\/p>');})(window,navigator,document);//]]>