Epidermal CFTR Suppresses MAPK/NF-κB to Promote Cutaneous Wound Healing

Abstract

Background: CFTR is implicated in cutaneous wound healing although the underlying mechanisms are not fully understood. In other cell types, CFTR is reported to regulate MAPK/ NF-κB signaling. We undertook the present study to explore a possible role of CFTR in regulating MAPK/NF-κB during cutaneous wound healing. Methods& Results: The splint-excisional and incisional wound healing models were used in CFTR mutant (DF508) mice. The cell-scratch model was used in a human keratinocyte line, HaCaT, in conjunction with CFTR knockdown or overexpression. The epidermal inflammation, keratinocyte proliferation and differentiation, as well as MAPK/NF-κB signaling were examined. Inhibitors of MAPK/NF-κB were also used. Results: Both DF508 mice and HaCaT cells with CFTR knockdown exhibited delayed cutaneous wound healing with exuberant inflammation, increased proliferation and aberrant differentiation. Knockdown of CFTR in HaCaT cells resulted in phosphorylation of ERK, p38 and IκBα. The disturbance of inflammation, proliferation and differentiation in HaCaT cells were reversed by CFTR overexpression or inhibition of MAPK or NF-κB. Conclusion: CFTR plays a role in suppressing MAPK/NF-κB to relieve inflammation, reduce proliferation and promote differentiation of keratinocytes, and thus promotes cutaneous wound healing.

Hereditary palmoplantar keratodermas. Part II: syndromic palmoplantar keratodermas – Diagnostic algorithm and principles of therapy

“…AWP has been reported as either recessive or dominant trait. It occurs in up to 84% of patients with CF, which is due to biallelic mutations in the CF transmembrane conductance regulator ( CFTR ) gene (Table ) and characterized by a classical diagnostic triad of chronic lung disease, exocrine pancreatic insufficiency and abnormally high salt concentration in the sweat. Sporadic AWP individuals, described as affected with non‐classic CF or without CF, were shown to carry monoallelic or biallelic mutations in the CFTR .…”

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

“…Various animal wound‐healing models have been successfully utilized to better understand the basic mechanisms of the acute wound‐healing process, and to some extent, its pathophysiology . The most commonly used animal models for wound healing, such as murine, rat, porcine and rabbit, are widely available and share important anatomical and physiological characteristics with the human wound‐healing process.…”

Porous Poly(Hexamethylene Biguanide) Hydrochloride Loaded Silk Fibroin Sponges with Antibacterial Function

“…SF has been shown to be promising as a wound dressing due to its excellent biocompatibility, biodegradability, and low immunogenicity [9,10]. When SF dressings cover a skin defect, the NF-kB signaling pathway can be stimulated to control the expression of vimentin, cyclin D1, vascular endothelial cell growth factor, and fibronectin [11][12][13][14], which regulate cell adhesion and proliferation [15] and enhance c-Jun protein expression and phosphorylation to promote wound healing [16]. The results of our previous studies have shown that three-dimensional SF scaffolds prepared by freeze-drying can guide the growth of capillaries, microvessels, and fibroblasts and promote the regeneration of dermal tissue [17][18][19].…”