Accelerated wound healing by mTOR activation in genetically defined mouse models

PLoS ONE

Volumn 5, Issue 5, 2010, Pages

  Squarize, Cristiane H ^a,b   Castilho, Rogerio M ^a,b   Bugge, Thomas H ^a   Gutkind, J Silvio ^a  

^a NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH   (United States)

^b UNIVERSITY OF MICHIGAN SCHOOL OF DENTISTRY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKERATIN 10; CYTOKERATIN 14; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; PROTEIN S6; RAPAMYCIN; SERINE; TUBERIN; PROTEIN SERINE THREONINE KINASE; PTEN PROTEIN, MOUSE; SIGNAL PEPTIDE; TUBEROUS SCLEROSIS COMPLEX 1 PROTEIN; TUMOR SUPPRESSOR PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; ENZYME ACTIVATION; EPITHELIUM CELL; KERATINOCYTE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; SKIN INJURY; UPREGULATION; WOUND CLOSURE; WOUND HEALING; ANIMAL; CELL COMPARTMENTALIZATION; CELL MOTION; DRUG EFFECT; ENZYMOLOGY; GENE DELETION; METABOLISM; PATHOLOGY; SKIN;

ANIMALS; CELL COMPARTMENTATION; CELL MOVEMENT; ENZYME ACTIVATION; EPITHELIAL CELLS; GENE DELETION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; KERATINOCYTES; MICE; MODELS, ANIMAL; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; SIROLIMUS; SKIN; TUMOR SUPPRESSOR PROTEINS; UP-REGULATION; WOUND HEALING;

EID: 77956283576     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0010643     Document Type: Article

References (42)

1. Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341: 738-746.
2. Ehrenreich M, Ruszczak Z (2006) Update on tissue-engineered biological dressings. Tissue Eng 12: 2407-2424.
3. Ashcroft GS, Mills SJ, Ashworth JJ (2002) Ageing and wound healing. Biogerontology 3: 337-345.
4. Ashcroft GS, Yang X, Glick AB, Weinstein M, Letterio JL, et al. (1999) Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol 1: 260-266.
5. Reynolds LE, Conti FJ, Lucas M, Grose R, Robinson S, et al. (2005) Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med 11: 167-174.
6. Schafer M, Werner S (2008) Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9: 628-638.
7. Cully M, You H, Levine AJ, Mak TW (2006) Beyond PTEN mutations: the PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer 6: 184-192.
8. Engelman JA (2009) Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 9: 550-562.
9. Hennessy BT, Smith DL, Ram PT, Lu Y, Mills GB (2005) Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 4: 988-1004.
10. Engelman JA, Luo J, Cantley LC (2006) The evolution of phosphatidylinositol 3- kinases as regulators of growth and metabolism. Nat Rev Genet 7: 606-619.
11. Keniry M, Parsons R (2008) The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 27: 5477-5485.
12. Sarret Y, Woodley DT, Grigsby K, Wynn K, O'Keefe EJ (1992) Human keratinocyte locomotion: the effect of selected cytokines. J Invest Dermatol 98: 12-16.
13. Ma XM, Blenis J (2009) Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10: 307-318.
14. Sabatini DM (2006) mTOR and cancer: insights into a complex relationship. Nat Rev Cancer 6: 729-734.
15. Castilho RM, Squarize CH, Chodosh LA, Williams BO, Gutkind JS (2009) mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell 5: 279-289.
16. Iijima M, Devreotes P (2002) Tumor suppressor PTEN mediates sensing of chemoattractant gradients. Cell 109: 599-610.
17. Comer FI, Parent CA (2007) Phosphoinositides specify polarity during epithelial organ development. Cell 128: 239-240.
18. Kunz J, Henriquez R, Schneider U, Deuter-Reinhard M, Movva NR, et al. (1993) Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73: 585-596.
19. Guertin DA, Sabatini DM (2007) Defining the role of mTOR in cancer. Cancer Cell 12: 9-22.
20. Sabers CJ, Martin MM, Brunn GJ, Williams JM, Dumont FJ, et al. (1995) Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem 270: 815-822.
21. Knight RJ, Villa M, Laskey R, Benavides C, Schoenberg L, et al. (2007) Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients. Clin Transplant 21: 460-465.
22. Kahan BD (2000) Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 356: 194-202.
23. Inoki K, Guan KL (2009) Tuberous sclerosis complex, implication from a rare genetic disease to common cancer treatment. Hum Mol Genet 18: R94-100.
24. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315: 1650-1659.
25. Squarize CH, Castilho RM, Gutkind JS (2008) Chemoprevention and treatment of experimental Cowden's disease by mTOR inhibition with rapamycin. Cancer Res 68: 7066-7072.
26. Kahan BD (2008) Fifteen years of clinical studies and clinical practice in renal transplantation: reviewing outcomes with de novo use of sirolimus in combination with cyclosporine. Transplant Proc 40: S17-20.
27. Raja, Sivamani K, Garcia MS, Isseroff RR (2007) Wound re-epithelialization: modulating keratinocyte migration in wound healing. Front Biosci 12: 2849-2868.
28. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M (2008) Growth factors and cytokines in wound healing. Wound Repair Regen 16: 585-601.
29. Nagy JA, Benjamin L, Zeng H, Dvorak AM, Dvorak HF (2008) Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 11: 109-119.
30. Mathew TH, Van Buren C, Kahan BD, Butt K, Hariharan S, et al. (2006) A comparative study of sirolimus tablet versus oral solution for prophylaxis of acute renal allograft rejection. J Clin Pharmacol 46: 76-87.
31. Campistol JM, Cockwell P, Diekmann F, Donati D, Guirado L, et al. (2009) Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation. Transpl Int 22: 681-687.
32. Schmid AC, Woscholski R (2004) Phosphatases as small-molecule targets: inhibiting the endogenous inhibitors of kinases. Biochem Soc Trans 32: 348-349.
33. Rosivatz E, Matthews JG, McDonald NQ, Mulet X, Ho KK, et al. (2006) A small molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN). ACS Chem Biol 1: 780-790.
34. Zhao M (2007) PTEN: a promising pharmacological target to enhance epithelial wound healing. Br J Pharmacol 152: 1141-1144.
35. Lai JP, Dalton JT, Knoell DL (2007) Phosphatase and tensin homologue deleted on chromosome ten (PTEN) as a molecular target in lung epithelial wound repair. Br J Pharmacol 152: 1172-1184.
36. Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355: 1345-1356.
37. Curatolo P, Bombardieri R, Jozwiak S (2008) Tuberous sclerosis. Lancet 372: 657-668.
38. Groszer M, Erickson R, Scripture-Adams DD, Lesche R, Trumpp A, et al. (2001) Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294: 2186-2189.
39. Meikle L, McMullen JR, Sherwood MC, Lader AS, Walker V, et al. (2005) A mouse model of cardiac rhabdomyoma generated by loss of Tsc1 in ventricular myocytes. Hum Mol Genet 14: 429-435.
40. Andl T, Ahn K, Kairo A, Chu EY, Wine-Lee L, et al. (2004) Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131: 2257-2268.
41. Romer J, Bugge TH, Pyke C, Lund LR, Flick MJ, et al. (1996) Plasminogen and wound healing. Nat Med 2: 725.
42. Castilho RM, Squarize CH, Patel V, Millar SE, Zheng Y, et al. (2007) Requirement of Rac1 distinguishes follicular from interfollicular epithelial stem cells. Oncogene 26: 5078-5085.