Das, AmitavaMadeshiya, Amit K.Biswas, NirupamGhosh, NandiniGorain, MahadeoRawat, AtulMahajan, Sanskruti P.Khanna, SavitaSen, Chandan K.Roy, Sashwati2023-11-022023-11-022022Das A, Madeshiya AK, Biswas N, et al. Oncostatin M Improves Cutaneous Wound Re-Epithelialization and Is Deficient under Diabetic Conditions. J Invest Dermatol. 2022;142(3 Pt A):679-691.e3. doi:10.1016/j.jid.2021.04.039https://hdl.handle.net/1805/36906Impaired re-epithelialization characterized by hyperkeratotic non-migratory wound epithelium is a hallmark of non-healing diabetic wounds. In chronic wounds, copious release of oncostatin M (OSM) from wound macrophages is evident. OSM is a potent keratinocyte activator. This work sought to understand the signal transduction pathway responsible for wound-re-epithelialization, the primary mechanism underlying wound closure. Daily topical treatment of full-thickness excisional wounds of C57bl/6 mice with recombinant murine OSM improved wound re-epithelialization and accelerated wound closure by bolstering keratinocyte proliferation and migration. OSM activated the JAK-STAT pathway as manifested by STAT3 phosphorylation. Such signal transduction in the human keratinocyte induced TP63, the master regulator of keratinocyte function. Elevated TP63 induced integrin beta 1, a known effector of keratinocyte migration. In diabetic wounds, OSM was more abundant compared to the level in non-diabetic wounds. However, in diabetic wounds OSM activity was compromised by glycation. Aminoguanidine, a deglycation agent, rescued compromised keratinocyte migration caused by glycated OSM. Finally, topical application of recombinant OSM improved keratinocyte migration and accelerated wound closure in db/db mice. This work recognizes that despite its abundance at the wound-site, OSM is inactivated by glycation and topical delivery of exogenous OSM is likely to be productive in accelerating diabetic wound closure.en-USPublisher PolicyOncostatin M (OSM)Re-epithelializationDiabetesp63IntegrinGlycationArticle