Ultraviolet B Downregulated Aquaporin 1 Expression via the MEK/ERK pathway in the Dermal Fibroblasts
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Background: Aquaporin 1 (AQP1) is a transmembrane channel protein that allows rapid transposition of water and gases, in recent discoveries of AQP1 function involve cell proliferation, differentiation, wound healing, inflammation and infection in different cell types, suggesting that AQP1 plays key roles in diverse biologic process. Until now, less is known about the function of AQP1 on ultraviolet radiation induced photoaged skin. Objective: In this study we set out to examine whether AQP1 expression may be influenced by repeated irradiation of ultraviolet B (UVB) in cultured dermal fibroblasts. Methods: To elucidate the function of AQP1 in skin photoaging, human dermal fibroblasts (HS68) were irradiated by a series of 4 sub-cytotoxic doses of UVB which are known as UV-induced cell premature senescence model. Reverse transcription polymerase chain reaction and Western blotting were conducted to detect AQP1 expression from different groups. Then, cells were transfected with AQP1-targeting small interfering RNA. The activities of signaling proteins upon UVB irradiation were investigated to determine which pathways are involved in AQP1 expression. Results: AQP1 expression was increased by 100 mJ/cm2 of UVB irradiation, but decreased by 200 mJ/cm2. Depletion of the AQP1 increased the apoptotic sensitivity of cells to UVB, as judged by upregulation of the p53, p21, poly (adenosine diphosphate [ADP]-ribose) polymerase and Bax together with the increased Bax/Bcl2 ratio. UVB induced downregulation of AQP1 was significantly attenuated by pretreatment with the MEK/ERK inhibitor (PD98059). Conclusion: We concluded that AQP1 expression was down-regulated by repeated exposure of UVB via MEK/ERK activation pathways. The AQP1 reduction by UVB lead to changes of physiological functions in dermal fibroblasts, which might be associated with the occurrence and development of UVB induced photoaging.
Abstract
Background: Aquaporin 1 (AQP1) is a transmembrane channel protein that allows rapid transposition of water and gases, in recent discoveries of AQP1 function involve cell proliferation, differentiation, wound healing, inflammation and infection in different cell types, suggesting that AQP1 plays key roles in diverse biologic process. Until now, less is known about the function of AQP1 on ultraviolet radiation induced photoaged skin. Objective: In this study we set out to examine whether AQP1 expression may be influenced by repeated irradiation of ultraviolet B (UVB) in cultured dermal fibroblasts. Methods: To elucidate the function of AQP1 in skin photoaging, human dermal fibroblasts (HS68) were irradiated by a series of 4 sub-cytotoxic doses of UVB which are known as UV-induced cell premature senescence model. Reverse transcription polymerase chain reaction and Western blotting were conducted to detect AQP1 expression from different groups. Then, cells were transfected with AQP1-targeting small interfering RNA. The activities of signaling proteins upon UVB irradiation were investigated to determine which pathways are involved in AQP1 expression. Results: AQP1 expression was increased by 100 mJ/cm2 of UVB irradiation, but decreased by 200 mJ/cm2. Depletion of the AQP1 increased the apoptotic sensitivity of cells to UVB, as judged by upregulation of the p53, p21, poly (adenosine diphosphate [ADP]-ribose) polymerase and Bax together with the increased Bax/Bcl2 ratio. UVB induced downregulation of AQP1 was significantly attenuated by pretreatment with the MEK/ERK inhibitor (PD98059). Conclusion: We concluded that AQP1 expression was down-regulated by repeated exposure of UVB via MEK/ERK activation pathways. The AQP1 reduction by UVB lead to changes of physiological functions in dermal fibroblasts, which might be associated with the occurrence and development of UVB induced photoaging.
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