siRNA-Mediated MELK Knockdown Induces Accelerated Wound Healing with Increased Collagen Deposition

Abstract

Skin wounds remain a significant problem for the healthcare system, affecting the clinical outcome, patients’ quality of life, and financial costs. Reduced wound healing times would improve clinical, economic, and social aspects for both patients and the healthcare system. Skin wound healing has been studied for years, but effective therapy that leads to accelerated wound healing remains to be discovered. This study aimed to evaluate the potential of MELK silencing to accelerate wound healing. A vectorless, transient knockdown of the MELK gene using siRNA was performed in a murine skin wound model. The wound size, total collagen, type 3 collagen, vessel size, vessel number, cell proliferation, cell apoptosis, number of mast cells, and immune infiltration by CD45, CD11b, CD45, and CD8a cells were evaluated. We observed that treatment with MELK siRNA leads to significantly faster wound closing associated with increased collagen deposition.

PDK4 facilitates fibroblast functions and diabetic wound healing through regulation of HIF‐1α protein stability and gene expression

“…Taken together, these data suggest that PDK4 activates HDFs through HIF‐1α. In vivo, we also employed siRNA to knock down Hif‐1α 31–33 . First, we tested the knockdown efficiency of si Hif‐1α in vivo (Figure S5A).…”

“…In vivo, we also employed siRNA to knock down Hif-1α. [31][32][33] First, we tested the knockdown efficiency of si Hif-1α in vivo (Figure S5A). Knock down of Hif-1α attenuates the positive effect of PDK4 on wound healing in diabetic mice (Figure S5B-D), along with granulation tissue thickness (Figure S5E,F) and collagen deposition (Figure S5G).…”