The absence of uPAR is associated with the progression of dermal fibrosis.
The fibrinolytic system is considered to play an important role in the degradation of extracellular matrices (ECM). However, the detailed mechanism regarding how this system affects fibrosis remains unclear. Urokinase-type plasminogen activator receptor (uPAR) not only functions as a proteinase receptor but also plays a role in cellular adhesion, differentiation, proliferation, and migration through intracellular signaling. To investigate the effect of uPAR on dermal fibrosis, the skin of wild-type mice was compared with uPAR-deficient (uPAR(-/-)) mice. The results showed that the absence of uPAR increases dermal thickness. In addition, collagen synthesis as well as the number of myofibroblasts was greater in the skin of uPAR(-/-) mice than in the skin of uPAR(+/+) mice. Moreover, we showed that the absence of uPAR attenuates the activity of matrix metalloproteinases (MMP)-2, 9 in the skin. In conclusion, this study suggests that the absence of uPAR not only regulates fibrosis-related gene expression and MMP activity but also results in ECM deposition. Therefore, the absence of uPAR induces dermal fibrosis. These findings provide new insights into the role of uPAR on dermal fibrosis.
Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's Collage of Liberal Arts, Kyoto, Japan. ykanno@dwc.doshisha.ac.jp
Yosuke
Y
Kanno
Aki
A
Kaneiwa
Misato
M
Minamida
Miho
M
Kanno
Kanji
K
Tomogane
Koji
K
Takeuchi
Kiyotaka
K
Okada
Shigeru
S
Ueshima
Osamu
O
Matsuo
Hiroyuki
H
Matsuno
D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D008954:Models, Biological; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000473:pathology*
D055293:Receptors, Urokinase Plasminogen Activator; D003094:Collagen