PTEN, a biomarker and a master mediator of non-healing venous leg ulcers, suppresses immune response, angiogenesis and lymphangiogenesis

Reduced inflammatory response resulting from impaired leukocyte transmigration and egression, with suppression of kinases’ activity, including AKT, ERK, JNK1/2, SRC, and PDGFR, underlines the non-healing VLU signature. Bioinformatic analyses pinpointed PTEN as a master regulator of these processes and signaling pathways. Indeed, increased PTEN was confirmed in non-healing compared to healing VLUs, both on scRNA-Seq and protein levels.

Functional in vivo murine studies confirmed that pharmacological PTEN inhibition enhanced immune response and proinflammatory signals, angiogenesis and lymphangiogenesis which resulted in accelerated wound closure. We identified PTEN as a master regulator of non-healing phenotype controlling multiple key processes responsible for impaired healing, underscoring its potential use as diagnostic and therapeutic target to promote wound closure in VLUs.