Conditional knockout of N-WASP in mouse fibroblast caused keratinocyte hyper proliferation and enhanced wound closure

Abstract

Neural-Wiskott Aldrich Syndrome Protein (N-WASP) is expressed ubiquitously, regulates actin polymerization and is essential during mouse development. We have previously shown that N-WASP is critical for cell-ECM adhesion in fibroblasts. To characterize the role of N-WASP in fibroblast for skin development, we generated a conditional knockout mouse model in which fibroblast N-WASP was ablated using the Cre recombinase driven by Fibroblast Specific Protein promoter (Fsp-Cre). N-WASPFKO (N-WASPfl/fl; Fsp-cre) were born following Mendelian genetics, survived without any visible abnormalities for more than 1 year and were sexually reproductive, suggesting that expression of N-WASP in fibroblast is not critical for survival under laboratory conditions. Histological sections of N-WASPFKO mice skin (13 weeks old) showed thicker epidermis with higher percentage of cells staining for proliferation marker (PCNA), suggesting that N-WASP deficient fibroblasts promote keratinocyte proliferation. N-WASPFKO mice skin had elevated collagen content, elevated expression of FGF7 (keratinocyte growth factor) and TGFβ signaling proteins. Wound healing was faster in N-WASPFKO mice compared to control mice and N-WASP deficient fibroblasts were found to have enhanced collagen gel contraction properties. These results suggest that N-WASP deficiency in fibroblasts improves wound healing by growth factor-mediated enhancement of keratinocyte proliferation and increased wound contraction in mice.

Liposomes with Silk Fibroin Hydrogel Core to Stabilize bFGF and Promote the Wound Healing of Mice with Deep Second‐Degree Scald

“…Staining proliferating cell nuclear antigen (PCNA) was further used to evaluate cell proliferation around scald wound (Figure S4A, Supporting Information). There are barely few of proliferated cells around the wounds in control group and SF‐LIP group.…”

The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing

“…It is highly desirable to create a micro‐environment that can prompt the recruitment of autologous keratinocytes from wound edges and facilitate their migration to achieve faster re‐epithelialization (Jain et al, ). The rate of keratinocyte migration depends on the cytokines released around the wound and the ECM under the wound (O'Toole, ; Tsuboi et al, ).…”

Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing

“…An increase in its expression is seen in fibroblast post injury, and previous reports suggest that FGF7 induces hyper proliferation of keratinocytes and enhanced wound closure ( Erdag et al, 2004 ). Increase in expression of FGF7 is found in N-WASP conditional knockout mice which shows hyper proliferation of keratinocytes and rapid wound closure via TGFβ signaling mechanism ( Jain et al, 2016 ). Expression of colony stimulating factors, CSF3 in particular, is also increased post Amn treatment.…”