Crucial role of fibroblast integrins alpha2 and beta1 in maintaining the structural and mechanical properties of the skin.
BACKGROUND
In vivo functions of integrins in dermis have been investigated using several types of genetically integrin deficient mice. However, there are few studies to clarify actual in vivo functions of integrins in the dermis using normal type animals.


OBJECTIVE
We investigated the actual in vivo functions of integrins in maintaining structural and mechanical properties in the normal skin by means of blocking interactions between fibroblasts and the extracellular matrix (ECM).


METHODS
Intradermal injection of anti-integrin alpha2 or beta1 antibody into hairless rat skin was used to block the function of integrins. The dermal thickness was measured by an ultrasound scanner and the elastic properties of the skin was measured by Cutometer.


RESULTS
Blocking integrin alpha2 or beta1 alone caused a moderate increase in dermal thickness. Blocking of integrins alpha1, alphaL or beta2 alone or blocking both integrins alpha1 and beta1 did not cause any change in the skin. However, blocking of both integrins alpha2 and beta1 caused a significant increase in dermal thickness accompanied by a marked loss of elastic properties. A clear change of the skin was observed within several minutes after injection, and continued for several hours. Treatment of human skin fibroblasts in collagen gel lattices with a mixture of anti-integrin alpha2 and beta1 antibodies in vitro caused marked and rapid morphological changes, but significant change was not observed with a treatment of alpha1, alpha2 or beta1 antibody alone.


CONCLUSIONS
These results indicate that simultaneous functioning of integrins alpha2 and beta1 in fibroblasts play a crucial role in maintaining the structural and mechanical properties in the skin, which suggests that fibroblasts actively regulate collagen networks via these integrins.
Fujimura
Tsutomu
T
Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai-machi, Haga-gun, Tochigi 321-3497, Japan. Fujimura.tsutomu@kao.co.jp <Fujimura.tsutomu@kao.co.jp>
Moriwaki
Shigeru
S
Imokawa
Genji
G
Takema
Yoshinori
Y
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003094:Collagen; D020405:Dermis / Q000000981:diagnostic imaging; D004338:Drug Combinations; D004357:Drug Synergism; D004548:Elasticity; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005782:Gels; D006801:Humans; D007271:Injections, Intradermal; D039423:Integrin alpha1 / Q000276:immunology / Q000502:physiology; D039421:Integrin alpha2 / Q000276:immunology / Q000502:physiology*; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology*; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012879:Skin Physiological Phenomena; D014463:Ultrasonography
D000906:Antibodies; D004338:Drug Combinations; D005782:Gels; D039423:Integrin alpha1; D039421:Integrin alpha2; D019012:Integrin beta1; D003094:Collagen