Thy-1 (CD90), Integrins and Syndecan 4 are Key Regulators of Skin Wound Healing

Abstract

Acute skin wound healing is a multistage process consisting of a plethora of tightly regulated signaling events in specialized cells. The Thy-1 (CD90) glycoprotein interacts with integrins and the heparan sulfate proteoglycan syndecan 4, generating a trimolecular complex that triggers bi-directional signaling to regulate diverse aspects of the wound healing process. These proteins can act either as ligands or receptors, and they are critical for the successful progression of wound healing. The expression of Thy-1, integrins, and syndecan 4 is controlled during the healing process, and the lack of expression of any of these proteins results in delayed wound healing. Here, we review and discuss the roles and regulatory events along the stages of wound healing that support the relevance of Thy-1, integrins, and syndecan 4 as crucial regulators of skin wound healing.

The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion

“…Wound healing is a complex multistage process involving many molecular interactions and signaling pathways that permit successful repair of the skin. Thy-1 has been considered a protein of interest in this process because its upregulation during the inflammatory stage has been associated with angiogenesis [ 16 , 17 ]. Here, we demonstrated that the lack of Thy-1 in mice retards the wound healing process and impairs re-epithelialization associated with decreased blood perfusion during the healing process.…”

“…The contraction would be different if the lesion were more extensive and if the location were in a place where the skin is looser (medium dorsum) or tighter (between the ears). Therefore, cells are affected by different mechanical forces, which are known to affect the responses of the Thy-1/integrin/syndecan-4 complex [ 17 ]. Unfortunately, the paper by Sedov et al did not discuss the differences between their findings and those previously reported by Lee and co-workers [ 18 ], which demonstrated the opposite effect caused by Thy-1 deficiency.…”

“…In recent years, increased emphasis has been granted to studying the role of Thy-1 and its downstream signaling pathways in wound healing [ 17 ]. Specifically, Lee and co-workers [ 18 ] investigated these events using Thy-1 knockdown in a mouse model of skin wound healing and showed that wound repair is retarded when Thy-1 levels are decreased.…”

“…So far, only a few studies have suggested a clear association between Thy-1 expression and angiogenesis [ 18 , 19 ]; these have reported that Thy-1 expression is crucial in the process of new vessel formation. We recently reviewed the role of Thy-1 and its receptors—integrins and Syndecan-4—in wound healing [ 17 ]. From this analysis of the literature, it became clear that the function of Thy-1 in the angiogenic process remains poorly understood.…”

Thy-1-Integrin Interactions in cis and Trans Mediate Distinctive Signaling

“…In the context of fibroblast-DC interaction, the Thy-1–integrin interaction might also play an important role in DC migration, since integrins are recognized players of cell migration. In this skin inflammatory model, IL-6 was recognized for the first time as a cytokine capable of inducing DC production of MMP9 and thus, as an important regulator of DC migration [see recent review on this topic in ( Perez, Leyton et al, 2022 )].…”