Akt1 controls insulin-driven VEGF biosynthesis from keratinocytes: Implications for normal and diabetes-impaired skin repair in mice

Journal of Investigative Dermatology

Volumn 129, Issue 3, 2009, Pages 752-764

  Goren, Itamar ^a   Müller, Elke ^a   Schiefelbein, Dana ^a   Gutwein, Paul ^a   Seitz, Oliver ^b   Pfeilschifter, Josef ^a   Frank, Stefan ^a,b  

^a Pharmazentrum Frankfurt   (Germany)

^b UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AKT1 PROTEIN; INITIATION FACTOR 4E BINDING PROTEIN 1; INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VASCULOTROPIN; WORTMANNIN;

ANIMAL MODEL; ARTICLE; CELL LINE; CHRONIC WOUND; CONTROLLED STUDY; DIABETES MELLITUS; DOWNSTREAM PROCESSING; FEMALE; GENE CONTROL; GENETIC TRANSFECTION; KERATINOCYTE; METABOLISM; MOUSE; MUTANT; NONHUMAN; NUCLEOTIDE SEQUENCE; POSTTRANSCRIPTIONAL GENE SILENCING; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REGULATORY MECHANISM; SKIN; SKIN CULTURE; TRANSLATION INITIATION; WOUND HEALING IMPAIRMENT;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; CARRIER PROTEINS; DIABETES MELLITUS; HUMANS; KERATINOCYTES; MICE; MICE, INBRED C57BL; MODELS, BIOLOGICAL; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; SKIN; VASCULAR ENDOTHELIAL GROWTH FACTOR A; WOUND HEALING;

EID: 59949086075     PISSN: 0022202X     EISSN: 15231747     Source Type: Journal    
DOI: 10.1038/jid.2008.230     Document Type: Article

References (45)

1. Andjelkovic M, Alessi DR, Meier R, Fernandez A, Lamb NJ, Frech M et al. (1997) Role of translocation in the activation and function of protein kinase B. J Biol Chem 272:31515-24
2. Apelqvist J, Larsson J, Agardh CD (1993) Long-term prognosis for diabetic patients with foot ulcers. J Intern Med 233:485-91.
3. Bachmann M, Hennemann H, Xing PX, Hoffmann I, Möröy T (2004) The oncogenic serine/threonine kinase Pim-1 phosphorylates and inhibits the activity of Cdc25C-associated kinase 1 (C-TAK1). J Biol Chem 279:48319-28
4. Boukamp P, Petrussevsak RT, Breitkreuz D, Hornung J, Markham A, Fusenig N (1988) Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol 106:761-71
5. Boulton AJM (2004) The diabetic foot: from art to science. The 18th Camillo Golgi lecture. Diabetologia 47:1343-53
6. Brown LF, Yeo KT, Berse B, Yeo TK, Senger DR, Dvorak HF et al. (1992) Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing. J Exp Med 176:1375-9
7. Calautti E, Li J, Saoncella S, Brisette JL, Goetinck PF (2005) Phosphoinositide 3-kinase signaling to Akt promotes keratinocyte differentiation versus death. J Biol Chem 280:32856-65
8. Carrington AL, Abbott CA, Griffiths J, Jackson N, van Ross ERE, Boulton AJM (2001) A foot care program for diabetic unilateral amputees. Diabetes Care 24:216-21
9. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156-9
10. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA (1995) Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785-9
11. Faglia E, Favales F, Morabito A (2001) New ulceration, new major amputation, and survival rates in diabetic subjects hospitalized for foot ulceration from 1990 to 1993: a 6.5 year follow-up. Diabetes Care 24:78-83
12. Frank S, Hübner G, Breier G, Longaker MT, Greenhalgh DG, Werner S (1995) Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem 270:12607-13
13. Frank S, Stallmeyer B, Kämpfer H, Kolb N, Pfeilschifter J (1999) Nitric oxide triggers enhanced induction of vascular endothelial growth factor expression in cultured keratinocytes (HaCaT) and during cutaneous wound repair. FASEB J 13:2002-14
14. Frank S, Stallmeyer B, Kämpfer H, Kolb N, Pfeilschifter J (2000) Leptin enhances wound re-epithelialization and constitutes a direct function of leptin in skin repair. J Clin Invest 106:501-9
15. Franke TF, Yang SI, Chan TO, Datta K, Kazlauskas A, Morrison DK et al. (1995) The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81:727-37
16. Gingras AC, Raught B, Sonenberg N (2001) Regulation of translation initiation by FRAP/mTOR. Genes Dev 15:807-26
17. Goren I, Kämpfer H, Podda M, Pfeilschifter J, Frank S (2003) Leptin and wound inflammation in diabetic ob/ob mice: differential regulation of neutrophil and macrophage influx and a potential role for the scab as a sink for inflammatory cells and mediators. Diabetes 52:2821-32
18. Goren I, Müller E, Pfeilschifter J, Frank S (2006) Severely impaired insulin signaling in chronic wounds of diabetic ob/ob mice. A potential role of tumor necrosis factor-α. Am J Pathol 168:765-77
19. Goren I, Müller E, Schiefelbein D, Christen U, Mühl H, Pfeilschifter J et al. (2007) Systemic anti-TNFalpha treatment restores diabetes-impaired skin repair in ob/ob mice by inactivation of macrophages. J Invest Dermatol 127:2259-67
20. He Z, Opland DM, Way KJ, Ueki K, Bodyak N, Kang PM et al. (2006) Regulation of vascular endothelial growth factor expression and vascularization in the myocardium by insulin receptor and PI3K/Akt pathways in insulin resistance and ischemia. Arterioscler Thromb Vasc Biol 26:787-93
21. Jiang ZY, He Z, King BL, Kuroki T, Opland DM, Suzuma K et al. (2003) Characterization of multiple signaling pathways of insulin in the regulation of vascular endothelial growth factor expression in vascular cells and angiogenesis. J Biol Chem 278:31964-71
22. Kämpfer H, Kalina U, Mühl H, Pfeilschifter J, Frank S (1999) Counter-regulation of interleukin-18 mRNA and protein expression during cutaneous wound repair. J Invest Dermatol 113:369-74
23. Kämpfer H, Pfeilschifter J, Frank S (2001) Expressional regulation of angiopoietin-1 and -2 and the Tie-1 and -2 receptor tyrosine kinases during cutaneous wound healing: a comparative study of normal and impaired repair. Lab Invest 81:361-73
24. Lauer G, Sollberg S, Cole M, Flamme I, Sturzebecher J, Mann K et al. (2000) Expression and proteolysis of VEGF is increased in chronic wounds. J Invest Dermatol 115:12-8
25. Loots MA, Lamme EN, Zeegelaar J, Mekkes JR, Bos JD, Middelkoop E (1998) Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. J Invest Dermatol 111:850-7
26. Martin P (1997) Wound healing - aiming for perfect tissue regeneration. Science 276:75-81
27. Pankow S, Bamberger C, Klippel A, Werner S (2006) Regulation of epidermal homeostasis and repair by phosphoinositide 3-kinase. J Cell Sci 119:4033-46
28. Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J et al. (2003) Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev 17:1352-65
29. Plas DR, Thompson CB (2005) Akt-dependent transformation: there is more to growth than just surviving. Oncogene 24:7435-42
30. Poulaki V, Mitsiades CS, McMullan C, Sykoutri D, Fanourakis G, Kotoula V et al. (2003) Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas. J Clin Endocrinol Metab 88:5392-8
31. Reiber GE, Ledoux WR (2002) Epidemiology of diabetic foot ulcers and amputations: evidence for prevention. In: The Evidence Base for Diabetes Care. (Williams R, Herman W, Kinmoth AL, Wareham NJ (eds). Wiley: Chichester, UK, 641-65
32. Roth D, Piekarek M, Paulsson M, Christ H, Krieg T, Bloch W et al. (2006) Plasmin modulates vascular endothelial growth factor-A-mediated angiogenesis during wound repair. Am J Pathol 168:670-84
33. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098-101
34. Schreiber E, Matthias P, Müller MM, Schaffner W (1989) Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res 17:6419
35. Segrelles C, Lu J, Hammann B, Santos M, Moral M, Cascallana JL et al. (2007) Deregulated activity of Akt in epithelial basal cells induces spontaneous tumors and heightened sensitivity to skin carcinogenesis. Cancer Res 67:10879-88
36. Segrelles C, Ruiz S, Perez P, Murga C, Santos M, Budunova IV et al. (2002) Functional roles of Akt signaling in mouse skin tumorigenesis. Oncogene 21:53-64
37. Segrelles C, Ruiz S, Santos M, Martinez-Palacio J, Lara MF, Paramio JM (2004) Akt mediates an angiogenic switch in transformed keratinocytes. Carcinogenesis 25:1137-47
38. Singer AJ, Clark RAF (1999) Cutaneous wound healing. N Engl J Med 341:728-46
39. Stallmeyer B, Kämpfer H, Kolb N, Pfeilschifter J, Frank S (1999) The function of nitric oxide in wound repair: inhibition of inducible nitric oxide synthase severely impairs wound reepithelialization. J Invest Dermatol 113:1090-8
40. Stallmeyer B, Pfeilschifter J, Frank S (2001) Systemically and topically supplemented leptin fails to reconstitute a normal angiogenic response during skin repair in diabetic ob/ob mice. Diabetologia 44:471-9
41. Testa JR, Tsichlis PN (2005) Akt signaling in normal and malignant cells. Oncogene 24:7391-3
42. Trash BR, Menges CW, Pierce RH, McCance DJ (2006) Akt1 provides an essential survival signal required for differentiation and stratification of primary human keratinocytes. J Biol Chem 281:12155-62
43. Treins C, Giorgetti-Peraldi S, Murdaca J, Semenza GL, Van Obberghen E (2002) Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 277:27975-81
44. Weindel K, Marme D, Weich HA (1992) AIDS-associated Kaposi's sarcoma cells in culture express vascular endothelial growth factor. Biochem Biophys Res Commun 183:1167-74
45. Wetzler C, Kämpfer H, Stallmeyer B, Pfeilschifter J, Frank S (2000) Large and sustained induction of chemokines during impaired wound healing in the genetically diabetic mouse: prolonged persistence of neutrophils and macrophages during the late phase of repair. J Invest Dermatol 115:245-52