Urokinase-type plasminogen activator negatively regulates α-smooth muscle actin expression via Endo180 and the uPA receptor in corneal fibroblasts.
Am J Physiol Cell Physiol
; 323(1): C104-C115, 2022 07 01.
Article
em En
| MEDLINE
| ID: mdl-35649252
ABSTRACT
Corneal fibroblasts are embedded within an extracellular matrix composed largely of collagen type 1, proteoglycans, and other proteins in the corneal stroma, and their morphology and function are subject to continuous regulation by collagen. During wound healing and in various pathological conditions, corneal fibroblasts differentiate into myofibroblasts characterized by the expression of α-smooth muscle actin (α-SMA). Endo180, also known as urokinase-type plasminogen activator (uPA) receptor-associated protein (uPARAP), is a collagen receptor. Here we investigated whether targeting of Endo180 and the uPA receptor (uPAR) by uPA might play a role in the regulation of α-SMA expression by culturing corneal fibroblasts derived from uPA-deficient (uPA-/-) or wild-type (uPA+/+) mice in a collagen gel or on plastic. The expression of α-SMA was upregulated, the amounts of full-length Endo180 and uPAR were increased, and the levels of both transforming growth factor-ß (TGF-ß) expression and Smad3 phosphorylation were higher in uPA-/- corneal fibroblasts compared with uPA+/+ cells under the collagen gel culture condition. Antibodies to Endo180 inhibited these effects of uPA deficiency on α-SMA and TGF-ß expression, whereas a TGF-ß signaling inhibitor blocked the effects on Smad3 phosphorylation and α-SMA expression. Our results suggest that uPA deficiency might promote the interaction between collagen and Endo180 and thereby increase α-SMA expression in a manner dependent on TGF-ß signaling. Expression of α-SMA is thus negatively regulated by uPA through targeting of Endo180 and uPAR.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ativador de Plasminogênio Tipo Uroquinase
/
Actinas
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Cell Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão