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

• Published in: Journal of cellular physiology Vol. 234; no. 8; pp. 12876 - 12883
• Main Authors: Farhadi, Elham, Mahmoudi, Mahdi, Rahmani, Farzaneh, Yousefi, Bahman, Sarafnejad, Abdolfattah, Kavosi, Hoda, Karimizadeh, Elham, Jamshidi, Ahmadreza, Gharibdoost, Farhad
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.08.2019
• Subjects: Activation; Adult; Aquaporin 3; Aquaporin 3 - genetics; Aquaporin 3 - metabolism; Aquaporins; Attenuation; Cells, Cultured; Dehydration; Epidermal growth factor; Epidermal Growth Factor - metabolism; epidermal growth factor receptor; Epidermal growth factor receptors; ErbB Receptors - metabolism; Female; Fibroblasts; Fibroblasts - metabolism; Gene expression; Growth factors; Humans; Male; Matrix metalloproteinase; Metalloproteinase; Middle Aged; mRNA; Patients; Polymerase chain reaction; Proteins; Scleroderma; Scleroderma, Systemic - metabolism; Signal Transduction - drug effects; Skin; skin fibroblast; Systemic sclerosis; Tissue inhibitor of metalloproteinase 1; Transforming growth factor; Transforming growth factor-b1; Wound healing; skin fibroblast; aquaporin-3; epidermal growth factor receptor; scleroderma
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27952

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. Downregulation of aquaporin‐3 (AQP3) expression in systemic sclerosis (SSc) fibroblasts may be related to reduced epidermal growth factor receptor (EGFR) expression and activation. Transforming growth factor‐β1 (TGF‐β1; alone or in combination with epidermal growth factor [EGF]) only can upregulate AQP3 expression in SSc fibroblasts so, TGF‐β1 affect MMP‐1 and MMP‐9 just in SSc fibroblasts.