Cellular Mechanisms Driving the Distinct Behavior of Trichocyte Keratins in Wound Healing

Trichocyte keratins hold significant promise in accelerating wound healing. Yet it is difficult to discriminate characteristics and mechanisms from their subtypes because of the high sequence homology. Here, the distinct wound healing properties in terms of wound closure rate, epidermal regeneration and angiogenesis of 17 kinds of human hair keratins is reported. Each trichocyte keratin shows distinct behaviors with unique advantages. Amongst all, recombinant keratin (RK) 33B, RK34, RK39 and RK84 show the highest efficiency in wound closure acceleration, and RK34, RK37 and RK81 presented the strongest angiogenic performance. Furthermore, transcriptomic analysis revealed the regulatory mechanisms of trichocyte keratins in the proliferation and migration of keratinocyte and blood vessel generation. Finally, the keratins with strong re-epithelialization and angiogenic performances significantly accelerate wound closure in a diabetic rat model established in-house. The findings provide a panorama view of trichocyte keratin performance in wound healing and that may harbor potential for finely tailored keratin development and precision applications. The significant variations in wound closure rate, angiogenesis, and re-epithelialization is found among 17 kinds of trichocyte keratins, which mediate the proliferation and migration of keratinocyte through PI3K/AKT1/mTOR signaling pathway, and blood vessel generations through the STAT3/HIF-1 & alpha;/VEGF signaling pathway. Furthermore, keratins with strong re-epithelialization and angiogenic performances significantly accelerate wound closure in a diabetic rat.image