Up-regulated type I collagen expression by the inhibition of Rac1 signaling pathway in human dermal fibroblasts.
Tissue remodeling is known to play important roles in wound healing. Although Rac1 is reported to be one of the key signaling molecules in cutaneous wound healing process, the exact mechanisms of Rac1-mediated tissue remodeling is still unknown. This study investigated the role of Rac1 in the regulation of extracellular matrix in cultured human dermal fibroblasts obtained by skin biopsy from three healthy donors. Protein levels of type I collagen in cultured human fibroblasts were increased by the treatment with Rac1 inhibitor NSC23766 in a dose-dependent manner. However, the mRNA levels of alpha2(I) collagen was not altered by the inhibitor. On the other hand, by the addition of inhibitor, half-lives of type I collagen protein were increased and MMP1 levels were reduced. These data suggest that blockade of Rac1 signaling results in accumulation of type I collagen due to decreased collagenase activity. This study also suggests that controlling Rac1 signaling is a new therapeutic approach to chronic/untreatable ulcer.
Igata
Toshikatsu
T
Department of Dermatology & Plastic Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Jinnin
Masatoshi
M
Makino
Takamitsu
T
Moriya
Chikako
C
Muchemwa
Faith C
FC
Ishihara
Tsuyoshi
T
Ihn
Hironobu
H
D000634:Aminoquinolines / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D024042:Collagen Type I; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D015854:Up-Regulation; D014945:Wound Healing; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000634:Aminoquinolines; D024042:Collagen Type I; C487513:NSC 23766; D011743:Pyrimidines; C107953:RAC1 protein, human; D012333:RNA, Messenger; D003094:Collagen; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D020830:rac1 GTP-Binding Protein