Exogenous Smad3 accelerates wound healing in a rabbit dermal ulcer model

被引:24
作者
Sumiyoshi, K
Nakao, A
Setoguchi, Y
Okumura, K
Ogawa, H
机构
[1] Univ Yamanashi, Dept Immunol, Fac Med, Yamanashi 4093898, Japan
[2] Juntendo Univ, Sch Med, Atopy Allergy Res Ctr, Tokyo 113, Japan
[3] Juntendo Univ, Sch Med, Dept Dermatol, Tokyo 113, Japan
[4] Juntendo Univ, Sch Med, Dept Resp Med, Tokyo 113, Japan
关键词
adenovector; fibroblast; Smad7;
D O I
10.1111/j.0022-202X.2004.22730.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Exogenous administration of transforming growth factor-beta (TGF-beta) improves wound healing by affecting cellular and molecular events involved in tissue repair. But mice with a deficiency of a key TGF-beta signaling intermediate, Smad3, paradoxically showed accelerated cutanenous wound healing, suggesting that endogenous Smad3 had inhibitory effect on cutaneous wound healing. Here we investigated the effect of exogenous expression of Smad3 in dermal fibroblasts on cutaneous wound healing. Subcutaneous injection of adenovirus-containing Smad3 complementary DNA (AdCMV-Smad3) targeting mainly dermal fibroblasts accelerated tissue repair following full-thickness dermal round wounds in rabbit ear as judged by the size of granulation tissue area, number of capillaries, and re-epithelialization rate of the wounds. Expressions of alpha-smooth muscle actin (alpha-SMA), vascular endothelial growth factor (VEGF), and fibroblast growth factor receptor were upregulated in the wounded area injected with AdCMV-Smad3. Consistent with the in vivo findings, overexpression of Smad3 induced alpha-SMA, VEGF, and TGF-beta1 expression and augmented chemotactic response in cultured dermal fibroblasts. Therefore, exogenous administration of Smad3 targeting dermal fibroblasts accelerated tissue repair in a rabbit dermal ulcer model by affecting fibroblast responses associated with wound healing. The results suggest that Smad3, when overexpressed in dermal fibroblasts, can promote wound healing.
引用
收藏
页码:229 / 236
页数:8
相关论文
共 23 条
[1]   Proliferation and mitogenic response to PDGF-BB of fibroblasts isolated from chronic venous leg ulcers is ulcer-age dependent [J].
Ågren, MS ;
Steenfos, HH ;
Dabelsteen, S ;
Hansen, JB ;
Dabelsteen, E .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1999, 112 (04) :463-469
[2]   Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response [J].
Ashcroft, GS ;
Yang, X ;
Glick, AB ;
Weinstein, M ;
Letterio, JJ ;
Mizel, DE ;
Anzano, M ;
Greenwell-Wild, T ;
Wahl, SM ;
Deng, CX ;
Roberts, AB .
NATURE CELL BIOLOGY, 1999, 1 (05) :260-266
[3]   Smads as transcriptional co-modulators [J].
Attisano, L ;
Wrana, JL .
CURRENT OPINION IN CELL BIOLOGY, 2000, 12 (02) :235-243
[4]   TRANSFORMING GROWTH-FACTOR-BETA-1 INDUCES ALPHA-SMOOTH MUSCLE ACTIN EXPRESSION IN GRANULATION-TISSUE MYOFIBROBLASTS AND IN QUIESCENT AND GROWING CULTURED FIBROBLASTS [J].
DESMOULIERE, A ;
GEINOZ, A ;
GABBIANI, F ;
GABBIANI, G .
JOURNAL OF CELL BIOLOGY, 1993, 122 (01) :103-111
[5]   Roles of bone morphogenetic protein type I receptors and smad proteins in osteoblast and chondroblast differentiation [J].
Fujii, M ;
Takeda, K ;
Imamura, T ;
Aoki, H ;
Sampath, TK ;
Enomoto, S ;
Kawabata, M ;
Kato, M ;
Ichijo, H ;
Miyazono, K .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (11) :3801-3813
[6]   Dermal fibroblasts from venous ulcers are unresponsive to the action of transforming growth factor-β 1 [J].
Hasan, A ;
Murata, H ;
Falabella, A ;
Ochoa, S ;
Zhou, L ;
Badiavas, E ;
Falanga, V .
JOURNAL OF DERMATOLOGICAL SCIENCE, 1997, 16 (01) :59-66
[7]   TGF-beta signalling from cell membrane to nucleus through SMAD proteins [J].
Heldin, CH ;
Miyazono, K ;
tenDijke, P .
NATURE, 1997, 390 (6659) :465-471
[8]   DIFFERENTIAL MODULATION OF BFGF RECEPTORS BY TGF-BETA IN ADULT SKIN, SCLERODERMA SKIN, AND NEWBORN FORESKIN FIBROBLASTS [J].
KIKUCHI, K ;
YAMAKAGE, A ;
SMITH, EA ;
LEROY, EC ;
TROJANOWSKA, M .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1992, 99 (02) :201-205
[9]   Fibroblasts from chronic wounds show altered TGF-β-signaling and decreased TGF-β type II receptor expression [J].
Kim, BC ;
Kim, HT ;
Park, SH ;
Cha, JS ;
Yufit, T ;
Kim, SJ ;
Falanga, V .
JOURNAL OF CELLULAR PHYSIOLOGY, 2003, 195 (03) :331-336
[10]   Combination of insulin-like growth factor (IGF)-I and IGF-binding protein-1 promotes fibroblast-embedded collagen gel contraction [J].
Lee, YR ;
Oshita, Y ;
Tsuboi, R ;
Ogawa, H .
ENDOCRINOLOGY, 1996, 137 (12) :5278-5283