RESUMEN
Fibrosis following injury leads to aberrant regeneration and incomplete functional recovery of skeletal muscle, but the lack of detailed knowledge about the cellular and molecular mechanisms involved hampers the design of effective treatments. Using state-of-the-art technologies, Murray et al. (2017) found that perivascular PDGFRß-expressing cells generate fibrotic cells in the skeletal muscle. Strikingly, genetic deletion of αv integrins from perivascular PDGFRß-expressing cells significantly inhibited skeletal muscle fibrosis without affecting muscle vascularization or regeneration. In addition, the authors showed that a small molecule inhibitor of αv integrins, CWHM 12, attenuates skeletal muscle fibrosis. From a drug-development perspective, this study identifies a new cellular and molecular target to treat skeletal muscle fibrosis.
Asunto(s)
Fibrosis/prevención & control , Integrina alfaV/química , Integrina alfaV/metabolismo , Músculo Esquelético/patología , Pericitos/patología , Animales , Fibrosis/metabolismo , Fibrosis/patología , Humanos , Músculo Esquelético/metabolismo , Pericitos/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismoRESUMEN
Healing is a vital response important for the re-establishment of the skin integrity following injury. Delayed or aberrant dermal wound healing leads to morbidity in patients. The development of therapies to improve dermal healing would be useful. Currently, the design of efficient treatments is stalled by the lack of detailed knowledge about the cellular and molecular mechanisms involved in wound healing. Recently, using state-of-the-art technologies, it was revealed that macrophages signal via GPNMB to mesenchymal stem cells, accelerating skin healing. Strikingly, transplantation of macrophages expressing GPNMB improves skin healing in GPNMB-mutant mice. Additionally, topical treatment with recombinant GPNMB restored mesenchymal stem cells recruitment and accelerated wound closure in the diabetic skin. From a drug development perspective, this GPNMB is a new candidate for skin healing.