Attenuation of aquaporin‐3 and epidermal growth factor receptor expression and activation in systemic sclerosis dermal fibroblasts

Abstract

Objectives Impaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin‐3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients. Methods Skin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects. The mRNA and/or protein expression levels of AQP3, EGFR/p‐EGFR, matrix metalloproteinase‐1/2/9 (MMP‐1/2/9), and tissue inhibitors of metalloproteinase‐1 (TIMP1) at baseline and after EGF and transforming growth factor‐β1 (TGF‐β1) treatment was evaluated in extracted fibroblasts using real‐time polymerase chain reaction and western blot analysis. Results SSc fibroblasts expressed lower AQP3 and EGFR, compared with normal fibroblasts. Normal fibroblasts increased AQP3 expression in response to EGF whereas AQP3 expression had no change in EGF‐treated‐SSc fibroblasts. Likewise, EGFR was activated in response to EGF in the normal group but not SSc group. Baseline expression of MMP‐1/2/9 and TIMP1 was not different between SSc and controls. EGF treatment did not result in alteration of any MMPs expression in either of the groups. Combination treatment resulted in a significant upregulation of MMP‐1 in normal fibroblasts compared with SSc fibroblasts, while in SSc fibroblasts MMP‐9 expression was upregulated in response to treatment with TGF‐β1 only. Conclusion Downregulation of AQP3 expression in SSc fibroblasts may be related to reduced EGFR expression and activation. TGF‐β1 (alone or in combination with EGF) only can upregulate AQP3 expression in SSc fibroblasts so, TGF‐β1 affect MMP‐1 and MMP‐9 just in SSc fibroblasts.

Autophagy protects from photoageing in skin fibroblasts

“…Numerous cases have been published regarding allergic contact dermatitis (ACD) caused by acrylates present in glucose sensors and insulin pumps, not only in adults [1][2][3] but also in the paediatric diabetic patient population. [4][5][6] The new glucose monitoring systems and insulin pumps are innovative instruments allowing patients with diabetes to optimize glycaemic control without the burden of repeated skin pricks. However, cutaneous adverse events may make their use impossible, depriving people with diabetes of the opportunity to benefit from this significant progress.…”

“…As a member of the aquaglyceroporin subfamily, AQP3 is also permeable to glycerol, which underlies its ability to mediate crucial epidermal processes such as hydration, elasticity maintenance, barrier integrity and wound healing 1 . Although most functional studies have been performed in the epidermis, where AQP3 expression extends from the basal layer up to the stratum spinosum, 2 AQP3 is also expressed, at a lower level, in dermal fibroblasts, where it is involved in a bleomycin‐induced fibrosis mouse model 3,4 …”

“…1 Although most functional studies have been performed in the epidermis, where AQP3 expression extends from the basal layer up to the stratum spinosum, 2 AQP3 is also expressed, at a lower level, in dermal fibroblasts, where it is involved in a bleomycin-induced fibrosis mouse model. 3,4 In this issue of the BJD, Xie et al present an original mechanism whereby both short-and long-term ultraviolet A (UVA) exposure can specifically alter AQP3 expression in skin fibroblasts, affecting autophagy signalling and consequently the ageing process in this lineage. 5 Although in epidermal keratinocytes AQP3 expression has been mainly shown as reduced by UV exposure, Xie et al discriminate between short-and long-term UVA exposure, supporting the concept that UVA can have opposing effects (depending on dose and timing) on deregulation of AQP3 expression in skin fibroblasts.…”

Interplay between Cell-Surface Receptors and Extracellular Matrix in Skin

“…The epidermal growth factor (EGF) receptor (EGFR) is a transmembrane protein that belongs to the EGFR family of receptor tyrosine kinases along with that also includes ErbB2, ErbB3, and ErbB4 [347]. In skin, it is expressed both in epidermal keratinocytes [348] as well as dermal fibroblasts [349], though is most highly abundant in proliferative basal epidermal layers [348].…”

A comparative study on the expression profile of aquaporin 3(AQP3) gene in the skin fibroblast cells of Barbari and Sirohi breeds of goat

“…Amplification Plots and Dissociation Curve for all reactions were analyzed for the presence of primer dimers or secondary structures or non-specific amplification. The relative expression of AQP3 was analyzed using 2 "ΔΔ Ct method by keeping GAPDH as the reference gene and 37°C in normal culture medium as the control sample (Farhadi et al, 2018;Livak & Schmittgen, 2001).…”