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Wound Fluid-derived Oncostatin M Induces P63 In Wound-edge Keratinocytes, Promotes Proliferation And Facilitates Wound Closure
Amitava Das, Atul Rawat, Nirupam Biswas, Nandini Ghosh, Savita Khanna, Chandan K. Sen and Sashwati Roy
Indiana Center for Regenerative Medicine and Engineering (ICRME)
2019-02-18
Presenter: Amitava Das
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: Chandan K. Sen
Author Category: Other Specialty Resident
Presentation Category: Basic Science Research
Abstract Category: General Reconstruction
Wound macrophages play multifaceted role in cutaneous wound healing. Emergent line of evidence argues in favor of a strong macrophage-keratinocyte cross-talk. This work builds on previous observation that human wound-site macrophages and wound fluid (WF) is rich in Oncostatin M (OSM) which primarily functions by its effect on keratinocytes. OSM is a known keratinocyte activator. Interestingly levels of OSM were significantly higher in WF from healing patients (>65% wound closure) than non-healing patients (<20% wound closure) (p˂0.05; n=6). We hypothesized that OSM produced by wound macrophages and present in the wound fluid interacts with wound-edge keratinocytes to drive keratinocyte cell proliferation towards healing. Human keratinocytes, when treated in vitro with human wound fluid (isolated from chronic wound patients), potently induced the expression of p63, a master regulator of epithelial development and differentiation (p˂0.05; n=5). Such an induction was inhibited significantly when OSM was neutralized (using neutralizing antibody) in WF, suggesting a role of WF OSM (p˂0.05; n=5). Treatment of human keratinocytes with recombinant OSM induced p63 and promoted keratinocyte proliferation (p˂0.05; n=4). Knockdown of p63 significantly blocked OSM-induced keratinocyte proliferation pointing towards a role of p63 in OSM-mediated keratinocyte proliferation (p˂0.05; n=4). Treatment of murine excisional wounds with recombinant OSM resulted in increased p63 expression in wound-edge keratinocytes, increased keratinocyte proliferation, improved re-epithelization and accelerated wound closure (p˂0.05; n=4). Taken together, this work upholds the critical significance of wound macrophage-keratinocyte cross talk in endowing the wound epithelium with higher proliferative potential.
