Integrin α11β1 as a Key Collagen Receptor in Human Skin Dermis: Insight into Fibroblast Function and Skin Dermal Aging

Abstract

Collagen-binding integrins play a crucial role in facilitating fibroblast–collagen interactions and regulating cellular functions. In this study, we identified that among 4 collagen-binding integrins, integrin α11 was the predominant type in human skin dermal fibroblasts and that loss of integrin α11 expression contributed to skin dermal aging. Integrin α11β1 was critical for regulating fibroblast–collagen interactions, including cell adhesion, spreading, morphology, mechanical tension, and the production of collagenous extracellular matrix. TGF-β was recognized as the primary regulator of integrin α11 expression. Notably, dermal fibroblasts in aged human skin demonstrated impaired TGF-β signaling, which coincided with a loss of integrin α11 expression, whereas the expression of other collagen-binding integrins remained unchanged. Similarly, in senescent dermal fibroblasts in vitro, impaired TGF-β signaling was associated with a significant reduction in integrin α11 expression, whereas other collagen-binding integrins were upregulated or unaffected. Furthermore, collapsed dermal fibroblasts, a key characteristic of dermal fibroblasts in aged human skin, specifically downregulated integrin α11, whereas other collagen-binding integrins were upregulated or remained unchanged. These findings suggest a negative feedback loop in which an impaired TGF-β–integrin α11β1 axis and fibroblast collapse promote dermal aging in human skin. This self-reinforcing cycle reflects the progressive and unidirectional nature of biological aging.