PTEN: a promising pharmacological target to enhance epithelial wound healing

Abstract

PI3Ks (phosphoinositide-3 kinases) produce PIP3 (phosphatidylinositol(3,4,5)-trisphosphate) which mediates signals for cell survival and proliferation. The tumour suppressor PTEN (phosphatase and tensin homologue) dephosphorylates PIP3 and is a key negative regulator of PI3K signalling. Recent research highlighted important roles for PI3K/PTEN in cell polarization and directional cell migration, pointing to a significant role for PTEN in wound healing where spatially organized tissue growth is essential. Lai et al. (in this issue of British Journal of Pharmacology) have moved a step closer in utilizing PTEN for wound healing through pharmacological inhibition. Two vanadium derivative inhibitors targeting PTEN significantly elevated the level of phosphorylated Akt (protein kinase B) and nearly doubled the wound healing rate in monolayer cultures of lung and airway epithelial cells. Damage to airway and lung epithelia underlies a wide spectrum of significant clinical conditions. With further experiments, this promising approach may find potential clinical use in situations where enhanced wound healing of pulmonary and other epithelia is important.

Figure 1

Pharmacologically targeting PTEN to enhance wound-healing response. Injury induces PI3K signalling, which activates Akt through production of PIP3 and stimulates wound-healing responses, such as cell migration, survival and proliferation. PTEN dephosphorylates the second messenger PIP3 and converts it back to the precursor PIP2, antagonizing the action of PI3K. Targeting PTEN (yellow polygon) with newly developed pharmacological inhibitors is a promising approach to facilitate PI3K signalling and wound healing. Dashed arrows omit many links.