Although humans and other mammals have lost, for the most part, the ability to regenerate injured tissue, the capacity to heal wounds is of critical importance for restoring function and, in the skin, maintaining a barrier against the external environment. The processes involved in wound healing include cleaning up the damaged tissue and preventing tissue invasion by microorganisms (inflammation), rebuilding the vascular network in the wounded site and creating a scaffold of connective tissue (granulation tissue formation), surfacing the wound (re-epithelialization), and a much slower process of re-organization of the scar. In some people, such as individuals with diabetes or venous stasis, the process goes awry and the wounds do not heal in a timely fashion or at all. Although tissue repair is effective in re-establishing a barrier, the wound healing process may lead to scarring, fibrosis, and loss of function (as in the case of contractures). Internal organs may similarly be scarred and the fibrosis and loss of architectural integrity may lead to significant organ dysfunction. Moreover, some illnesses, such as scleroderma, are characterized by pathologic fibrosis of the skin and/or internal organs resulting in diffuse skin fibrosis and internal organ dysfunction. Many other ailments, such as liver cirrhosis, may lead to specific organ destruction with resulting fibrosis, scarring, and loss of function.
A variety of factors regulate the wound healing process, ranging from growth factors to small molecules released at the wounded site. One such factor is adenosine, a ubiquitous purine nucleoside that is generated in the extracellular space by dephosphorylation of adenine nucleotides released by cells as a result of metabolic factors, injury, and hypoxia (). Adenosine mediates its effects on tissue regeneration and repair via binding and activation of a family of G protein-coupled receptors (adenosine A1, A2A, A2B, and A3 receptors). In this review, we will discuss the role of adenosine and its receptors in wound healing, fibrosis, and scarring.
Formation of adenosine from adenine nucleotides