The Signaling Mechanism Of Activin B And Quetiapine In The Regulation Of UVB-induced Skin Damage

BackgroundSkin is the most lateral and largest organ in the human body.As a protective barrier which directly contacts with external environment,the skin suffers from all kinds of injuries,including ultraviolet light damage and so on.And growth factors play an important role in the UV regulation of melanocyte.This study focused on activin B,a member of the TGF-β superfamily,to investigate the role in the process of UVB damage and its effect on the function of melanocytes.On the other hand,the role of quetiapine in the process of ultraviolet damage to the skin is explored from the perspective of "new use of the old drug" and the regulatory mechanisms that may be involved are explored,seeking more possibilities for the treatment and early prevention of photodamage.ObjectivePreliminary studying the mechanism of Activin B and quetiapine involved in the regulation of UVB-induced skin damage.MethodsIn our study,we isolated and cultured mouse melanocyte which were identified by immunofluorescence;We used the Elisa and Western blot to detect the influence of UVB on Activin B secretion and expression in keratinocytes;We used the NaOH method to detect the influence of Activin B on melanogenesis in melanocytes;Phalloidin staining was used to observe the effect of Activin B on dendritic changes,including the number,the width and the length;We used the CCK-8 method to detect the proliferation effect of Activin B on melanocytes;And we also used the Western blot to study the mechanism of melanogenesis regulated by Activin B.In order to elucidate the signaling mechanism of quetiapine in the skin damage induced by UVB,we established the acute light injury model in Kunming mice at the animal level;we established the light damage models using keratinocytes at the cellular level;cell proliferation was detected by CCK-8;LDH methods was used to detect the cell toxicity of quetiapine;secretion of oxidative stress related enzymes were detected by ELISA;using H&E,Masson staining to detect the affect of quetiapine on morphology and collagen secretion of skin tissue;F4/80 immunohistochemistry was used to detect the tissue inflammation;Western blot was used to study the signal mechanism of quetiapine in UVB induced skin damage.ResultsUVB can promote the secretion of Activin B in keratinocyte;Activin B can promote the synthesis and secretion of melanin,the proliferation of melanocyte and change the number and width of the dendritic;Activin B regulated the melanin synthesis of melanocyte through the ERK-PAX3 pathway.In vitro,quetiapine can enhance the anti-oxygenic of keratinocytes by strengthening their anti-oxygenic enzyme activity,including the SOD and GSH-Px,and decreasing the expression of MDA;In vivo,quetiapine can protect the skin from the damage caused by UVB by strengthening the activity of SOD and GSH-Px,decreasing the expression of MDA,and reducing the inflammatory response.Quetiapine may protect the skin from light damage induced by UVB through the p38 signal.ConclusionActivin B mediates the biological process of melanogenesis through ERK-PAX3 signaling pathway,and also participates in the UVB radiation process.Quetiapine could decrease acute light injury of skin damage induced by UVB irradiation through p38 MAPK signaling pathway.