Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes. The integrin family is composed of 24 αβ heterodimeric members that mediate the attachment of cells to the extracellular matrix (ECM) but that also take part in specialized cell-cell interactions. Only a subset of integrins (8 out of 24) recognizes the RGD sequence in the native ligands. In some ECM molecules, such as collagen and certain laminin isoforms, the RGD sequences are exposed upon denaturation or proteolytic cleavage, allowing cells to bind these ligands by using RGD-binding receptors. Proteolytic cleavage of ECM proteins might also generate fragments with novel biological activity such as endostatin, tumstatin, and endorepellin. Nine integrin chains contain an αI domain, including the collagen-binding integrins α1β1, α2β1, α10β1, and α11β1. The collagen-binding integrins recognize the triple-helical GFOGER sequence in the major collagens, but their ability to recognize these sequences in vivo is dependent on the fibrillar status and accessibility of the interactive domains in the fibrillar collagens. The current review summarizes some basic facts about the integrin family including a historical perspective, their structure, and their ligand-binding properties.

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The integrins form a large family of cell adhesion receptors. All multicellular animals express integrins, indicating that the family evolved relatively early in the history of metazoans, and homologous sequences of the component domains of integrin alpha and beta subunits are seen in prokaryotes. Some integrins, however, seem to be much younger. For example, the alphaI domain containing integrins, including collagen receptors and leukocyte integrins, have been found in chordates only. Here, we will discuss what conclusions can be drawn about integrin function by studying the evolutionary conservation of integrins. We will also look at how studying integrins in organisms such as the fruit fly and mouse has helped our understanding of integrin evolution-function relationships. As an illustration of this, we will summarize the current understanding of integrin involvement in skeletal muscle formation.

Previous wound healing studies have failed to define a role for either α1β1 or α2β1 integrin in fibroblast-mediated wound contraction, suggesting the involvement of another collagen receptor in this process. Our previous work demonstrated that the integrin subunit α11 is highly induced during wound healing both at the mRNA and protein level, prompting us to investigate and dissect the role of the integrin α11β1 during this process. Therefore, we used mice with a global ablation of either α2 or α11 or both integrin subunits and investigated the repair of excisional wounds. Analyses of wounds demonstrated that α11β1 deficiency results in reduced granulation tissue formation and impaired wound contraction, independently of the presence of α2β1. Our combined in vivo and in vitro data further demonstrate that dermal fibroblasts lacking α11β1 are unable to efficiently convert to myofibroblasts, resulting in scar tissue with compromised tensile strength. Moreover, we suggest that the reduced stability of the scar is a consequence of poor collagen remodeling in α11−/− wounds associated with defective transforming growth factor-β–dependent JNK signaling.