Transforming Growth Factor Beta 3 Is Required for Excisional Wound Repair In Vivo

被引:70
作者
Le, Mark [1 ]
Naridze, Rachelle [1 ]
Morrison, Jasmine [1 ]
Biggs, Leah C. [1 ]
Rhea, Lindsey [1 ]
Schutte, Brian C. [2 ]
Kaartinen, Vesa [3 ]
Dunnwald, Martine [1 ]
机构
[1] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA
[2] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA
[3] Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA
来源
PLOS ONE | 2012年 / 7卷 / 10期
基金
美国国家卫生研究院;
关键词
SCAR TISSUE FORMATION; TGF-BETA; EMBRYONIC-DEVELOPMENT; EXPRESSION PATTERNS; KNOCKOUT MICE; CLEFT-PALATE; P38; MAPK; TGF-BETA-3; SKIN; MOUSE;
D O I
10.1371/journal.pone.0048040
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Wound healing is a complex process that relies on proper levels of cytokines and growth factors to successfully repair the tissue. Of particular interest are the members of the transforming growth factor family. There are three TGF-beta isoforms-TGF beta 1, 2, and 3, each isoform showing a unique expression pattern, suggesting that they each play a distinct function during development and repair. Previous studies reported an exclusive role for TGF-beta 3 in orofacial development and a potent anti-scarring effect. However, the role of TGF-beta 3 in excisional wound healing and keratinocyte migration remains poorly understood. We tested the effect of TGF-beta 3 levels on excisional cutaneous wounds in the adult mouse by directly injecting recombinant TGF-beta 3 or neutralizing antibody against TGF-beta 3 (NAB) in the wounds. Our results demonstrate that TGF-beta 3 does not promote epithelialization. However, TGF-beta 3 is necessary for wound closure as wounds injected with neutralizing antibody against TGF-beta 3 showed increased epidermal volume and proliferation in conjunction with a delay in keratinocyte migration. Wild type keratinocytes treated with NAB and Tgfb3-deficient keratinocytes closed an in vitro scratch wound with no delay, suggesting that our in vivo observations likely result from a paracrine effect.
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页数:10
相关论文
共 49 条
  • [1] Amendt C, 2002, J CELL SCI, V115, P2189
  • [2] Keratinocyte regulation of TGF-β and connective tissue growth factor expression:: A role in suppression of scar tissue formation
    Amjad, Syed Basith
    Carachi, Robert
    Edward, Michael
    [J]. WOUND REPAIR AND REGENERATION, 2007, 15 (05) : 748 - 755
  • [3] Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
    Ashcroft, GS
    Yang, X
    Glick, AB
    Weinstein, M
    Letterio, JJ
    Mizel, DE
    Anzano, M
    Greenwell-Wild, T
    Wahl, SM
    Deng, CX
    Roberts, AB
    [J]. NATURE CELL BIOLOGY, 1999, 1 (05) : 260 - 266
  • [4] Mammary serine protease inhibitor (maspin) binds directly to interferon regulatory factor 6 - Identification of a novel serpin partnership
    Bailey, CM
    Khalkhali-Ellis, Z
    Kondo, S
    Margaryan, NV
    Seftor, REB
    Wheaton, WW
    Amir, S
    Pins, MR
    Schutte, BC
    Hendrix, MJC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (40) : 34210 - 34217
  • [5] A "traffic control" role for TGFβ3:: orchestrating dermal and epidermal cell motility during wound healing
    Bandyopadhyay, B
    Fan, JH
    Guan, SX
    Li, Y
    Chen, M
    Woodley, DT
    Li, W
    [J]. JOURNAL OF CELL BIOLOGY, 2006, 172 (07) : 1093 - 1105
  • [6] Baum CL, 2005, DERMATOL SURG, V31, P674
  • [7] Biggs L.C., 2011, J INVEST DERMATOL
  • [8] Delayed wound healing in immunodeficient TGF-β1 knockout mice
    Crowe, MJ
    Doetschman, T
    Greenhalgh, DG
    [J]. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (01) : 3 - 11
  • [9] Prophylactic administration of avotermin for improvement of skin scarring: three double-blind, placebo-controlled, phase I/II studies
    Ferguson, Mark W. J.
    Duncan, Jonathan
    Bond, Jeremy
    Bush, James
    Durani, Piyush
    So, Karen
    Taylor, Lisa
    Chantrey, Jonquille
    Mason, Tracey
    James, Gaynor
    Laverty, Hugh
    Occleston, Nick L.
    Sattar, Abdul
    Ludlow, Anna
    O'Kane, Sharon
    [J]. LANCET, 2009, 373 (9671) : 1264 - 1274
  • [10] Fowlis DJ, 1996, CELL GROWTH DIFFER, V7, P679