Connexin43 carboxyl-terminal peptides reduce scar progenitor and promote regenerative healing following skin wounding

Regenerative Medicine

Volumn 4, Issue 2, 2009, Pages 205-223

  Ghatnekar, Gautam S ^a,b   O'Quinn, Michael P ^a   Jourdan, L Jane ^a   Gurjarpadhye, Abhijit A ^a   Draugh, Robert L ^c   Gourdie, Robert G ^a,c  

^a MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^b FirstString Research Inc   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

Author keywords

Cx43; Gap junctions; Regenerative medicine; Scar prevention; Wound healing

Indexed keywords

CONNEXIN 43; PEPTIDE FRAGMENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL DENSITY; DRUG MECHANISM; EPIDERMIS; GRANULATION TISSUE; MOUSE; NEUTROPHIL; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN LOCALIZATION; REGENERATION; SCAR FORMATION; SKIN BLOOD FLOW; SKIN INJURY; TENSILE STRENGTH; WOUND CLOSURE; WOUND HEALING; ANIMAL; DRUG EFFECT; INJURY; PATHOLOGY; SCAR; SKIN; SWINE;

ANIMALS; CICATRIX; CONNEXIN 43; MICE; PEPTIDE FRAGMENTS; REGENERATION; SKIN; SWINE; WOUND HEALING;

EID: 65549168273     PISSN: 17460751     EISSN: None     Source Type: Journal    
DOI: 10.2217/17460751.4.2.205     Document Type: Article

References (55)

1. Bukauskas FF, Verselis VK: Gap junction channel gating. Biochim. Biophys. Acta 1662(1-2), 42-60 (2004).
2. Jean-Claude H: The connexins. Biochim. Biophys. Acta 1662(1-2), 1-2 (2004).
3. Willecke K, Eiberger J, Degen J et al.: Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 383(5), 725-737 (2002).
4. Chanson M, Derouette JP, Roth I et al.: Gap junctional communication in tissue inflammation and repair. Biochim. Biophys. Acta 1711(2), 197-207 (2005).
5. Bates DC, Sin WC, Aftab Q, Naus CC: Connexin43 enhances glioma invasion by a mechanism involving the carboxy terminus. Glia 55(15), 1554-1564 (2007).
6. De Maio A, Vega VL, Contreras JE: Gap junctions, homeostasis, and injury. J. Cell Physiol. 191(3), 269-282 (2002).
7. King TJ, Lampe PD: Temporal regulation of connexin phosphorylation in embryonic and adult tissues. Biochim. Biophys. Acta 1719(1-2), 24-35 (2005).
8. Lin JH, Weigel H, Cotrina ML et al.: Gap-junction-mediated propagation and amplification of cell injury. Nat. Neurosci. 1(6), 494-500 (1998).
9. Ehrlich HP, Sun B, Saggers GC, Kromath F: Gap junction communications influence upon fibroblast synthesis of Type I collagen and fibronectin. J. Cell Biochem. 98(4), 735-743 (2006).
10. Rhett JM, Ghatnekar GS, Palatinus JA, et al.: Novel therapies for scar reduction and regenerative healing of skin wounds. Trends Biotechnol. 26(4), 173-180 (2008).
11. Lin JH, Yang J, Liu S et al.: Connexin mediates gap junction-independent resistance to cellular injury. J. Neurosci. 23(2), 430-441 (2003).
12. Djalilian AR, McGaughey D, Patel S et al.: Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response. J. Clin. Invest 116(5), 1243-1253 (2006).
13. Kretz M, Maass K, Willecke K: Expression and function of connexins in the epidermis, analyzed with transgenic mouse mutants. Eur. J. Cell Biol. 83(11-12), 647-654 (2004).
14. Qiu C, Coutinho P, Frank S et al.: Targeting connexin43 expression accelerates the rate of wound repair. Curr. Biol. 13(19), 1697-1703 (2003).
15. Saitoh M, Oyamada M, Oyamada Y, Kaku T, Mori M: Changes in the expression of gap junction proteins (connexins) in hamster tongue epithelium during wound healing and carcinogenesis. Carcinogenesis 18(7), 1319-1328 (1997).
16. Coutinho P, Qiu C, Frank S, Tamber K, Becker D: Dynamic changes in connexin expression correlate with key events in the wound healing process. Cell Biol. Int. 27(7), 525-541 (2003).
17. Richards TS, Dunn CA, Carter WG, Usui ML, Olerud JE, Lampe PD: Protein kinase C spatially and temporally regulates gap junctional communication during human wound repair via phosphorylation of connexin43 on serine368. J. Cell Biol. 167(3), 555-562 (2004).
18. Risek B, Klier FG, Gilula NB: Multiple gap junction genes are utilized during rat skin and hair development. Development 116(3), 639-651 (1992).
19. Richard G, Smith LE, Bailey RA et al.: Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis. Nat. Genet. 20(4), 366-369 (1998).
20. Di WL, Common JE, Kelsell DP: Connexin 26 expression and mutation analysis in epidermal disease. Cell Commun. Adhes. 8(4-6), 415-418 (2001).
21. Mori R, Power KT, Wang CM, Martin P, Becker DL: Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration. J. Cell Sci. 119(Pt 24), 5193-5203 (2006).
22. Wang CM, Lincoln J, Cook JE, Becker DL: Abnormal connexin expression underlies delayed wound healing in diabetic skin. Diabetes 56(11), 2809-2817 (2007).
23. Dai P, Nakagami T, Tanaka H, Hitomi T, Takamatsu T: Cx43 mediates TGF-β signaling through competitive Smads binding to microtubules. Mol. Biol. Cell 18(6), 2264-2273 (2007).
24. Hunter AW, Barker RJ, Zhu C, Gourdie RG: Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol. Biol. Cell 16(12), 5686-5698 (2005).
25. Mitic LL, Anderson JM: Molecular architecture of tight junctions. Annu. Rev. Physiol. 60, 121-142 (1988).
26. Itoh M, Nagafuchi A, Moroi S, Tsukita S: Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to α catenin and actin filaments. J. Cell Biol. 138(1), 181-192 (1997).
27. Taliana L, Benezra M, Greenberg RS, Masur SK, Bernstein AM: ZO-1: lamellipodial localization in a corneal fibroblast wound model. Invest. Ophthalmol. Vis. Sci. 46(1), 96-103 (2005).
28. Gourdie RG, Ghatnekar GS, O'quinn M et al.: The unstoppable connexin43 carboxyl-terminus: new roles in gap junction organization and wound healing. Ann. NY Acad. Sci. 1080, 49-62 (2006).
29. Kyriakides TR, Tam JW, Bornstein P: Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene. J. Invest Dermatol. 113(5), 782-787 (1999).
30. Hewett KW, Norman LW, Sedmera D et al.: Knockout of the neural and heart expressed gene HF-1β results in apical deficits of ventricular structure and activation. Cardiovasc. Res. 67(3), 548-560 (2005).
31. Gourdie RG, Orwin DFG, Ranford S, Ross DA: Wool fibre tenacity and its relationship to staple strength. Aust. J. Agric. Res. 43(8), 1759-1776 (1992).
32. Churchill-Livingstone. Gray's Anatomy: The Anatomical Basis of Medicine and Surgery (2004).
33. Xie Y, Zhu KQ, Deubner H et al.: The microvasculature in cutaneous wound healing in the female red Duroc pig is similar to that in human hypertrophic scars and different from that in the female Yorkshire pig. J. Burn Care Res. 28(3), 500-506 (2007).
34. Ashcroft GS, Yang X, Glick AB et al.: Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat. Cell Biol. 1(5), 260-266 (1999).
35. Bandyopadhyay B, Fan J, Guan S et al.: A "traffic control" role for TGFβ3: orchestrating dermal and epidermal cell motility during wound healing. J. Cell Biol. 172(7), 1093-1105 (2006).
36. Coutinho P, Qiu C, Frank S et al.: Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury. Br. J. Plast. Surg. 58(5), 658-667 (2005).
37. Ferguson MW, O'Kane S: Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 359(1445), 839-850 (2004).
38. Martin P, D'Souza D, Martin J et al.: Wound healing in the PU.1 null mouse - tissue repair is not dependent on inflammatory cells. Curr. Biol. 13(13), 1122-1128 (2003).
39. Qiu C, Coutinho P, Frank S et al.: Targeting connexin43 expression accelerates the rate of wound repair. Curr. Biol. 13(19), 1697-1703 (2003).
40. Rhett JM, Ghatnekar GS, Palatinus JA et al.: Novel therapies for scar reduction and regenerative healing of skin wounds. Trends Biotechnol. 26(4), 173-180 (2008).
41. Clark R: Wound repair overview and general considerations. In: The Molecular and Cellular Biology of Wound Repair. Clark R (Ed.). Plenum Press, 3-50 (1996).
42. Dovi JV, He LK, DiPietro LA: Accelerated wound closure in neutrophil-depleted mice. J. Leukoc. Biol. 73(4), 448-455 (2003).
43. Stramer BM, Mori R, Martin P: The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during wound repair. J. Invest Dermatol. 127(5), 1009-1017 (2007).
44. Wang J, Jiao H, Stewart TL et al.: Accelerated wound healing in leukocyte-specific, protein 1-deficient mouse is associated with increased infiltration of leukocytes and fibrocytes. J. Leukoc. Biol. 82(6), 1554-1563 (2007).
45. Amadeu T, Braune A, Mandarim-de-Lacerda C, Porto LC, Desmouliere A, Costa A: Vascularization pattern in hypertrophic scars and keloids: a stereological analysis. Pathol. Res. Pract. 199(7), 469-473 (2003).
46. Gilchrest BA: A review of skin ageing and its medical therapy. Br. J. Dermatol. 135(6), 867-875 (1996).
47. Dang X, Doble BW, Kardami E: The carboxy-tail of connexin-43 localizes to the nucleus and inhibits cell growth. Mol. Cell Biochem. 242(1-2), 35-38 (2003).
48. Giepmans BN: Role of connexin43-interacting proteins at gap junctions. Adv. Cardiol. 42, 41-56 (2006).
49. Prochiantz A: Homeodomain-derived peptides. In and out of the cells. Ann. NY Acad. Sci. 886, 172-179 (1999).
50. Lindsey ML, Escobar GP, Mukherjee R et al.: Matrix metalloproteinase-7 affects connexin-43 levels, electrical conduction, and survival after myocardial infarction. Circulation 113(25), 2919-2928 (2006).
51. Maass K, Shibayama J, Chase SE, Willecke K, Delmar M: C-terminal truncation of connexin43 changes number, size, and localization of cardiac gap junction plaques. Circ. Res. 101(12), 1283-1291 (2007).
52. Hunter AW, Jourdan J, Gourdie RG: Fusion of GFP to the carboxyl terminus of connexin43 increases gap junction size in HeLa cells. Cell Commun. Adhes. 10(4-6), 211-214 (2003).
53. Hirschi KK, Burt JM, Hirschi KD, Dai C: Gap junction communication mediates transforming growth factor-β activation and endothelial-induced mural cell differentiation. Circ. Res. 93(5), 429-437 (2003).
54. Boengler K, Dodoni G, Rodriguez-Sinovas A et al.: Connexin43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning. Cardiovasc Res. 67(2), 234-244 (2005).
55. Fauza DO, Fishman SJ, Mehegan K, Atala A: Videofetoscopically assisted fetal tissue engineering: skin replacement. J. Pediatr. Surg. 33(2), 357-361 (1998).