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Geniposide inhibited endothelial-mesenchymal transition via the mTOR signaling pathway in a bleomycin-induced
Qing Qi1, Yueping Mao2, Yongzhen Tian3
1Department of Dermatology, The First Affiliated Hospital, Guangzhou University of Chinese MedicineGuangzhou 510405, China; Division of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, University of Texas Health Science Center at HoustonHouston 77030, Texas, USA.
Aim:
Geniposide is an iridoid glycoside isolated from the gardenia plant. It has multiple biological activities. The roles of geniposide in systemic sclerosis (SSc) and in endothelial-to-mesenchymal transition (EndMT) are unclear. We investigated the protective effects of geniposide in a bleomycin-induced SSc mouse model, and its potential mechanisms.
Methods:
The effects of geniposide were evaluated as follows: (1) histological and immunochemical changes in mouse skin tissue; (2) changes in cellular morphology of human umbilical vein endothelial cells (HUVECs); (3) expression of endothelial cell biomarkers (E-Cadherin, CD31, and CD34), mesenchymal cell markers (FSP1, Collagen, and α-SMA), and key factors of EndMT (Slug, Snail, and Twist) using real time PCR, Western blot, and immunofluorescence; (4) tube formation in HUVECs; (5) mTOR signaling pathway transcription factors using Western blot analysis.
Results:
Treatment with bleomycin induced up-regulation of mesenchymal cell biomarkers and down-regulation of endothelial cell biomarkers in in vivo and in vitro bleomycin-induced scleroderma models. Geniposide treatment suppressed these effects. Geniposide remedied bleomycin-induced dermal capillary loss and fibrosis in mice. The expression of key EndMT factors (Slug, Snail, and Twist) and the mTOR signaling pathway (mTOR and S6) were also attenuated by geniposide treatment.
Conclusion:
Geniposide had protective effects on endothelial cells in the bleomycin-induced scleroderma mouse model. These effects may occur via inhibition of the mTOR signaling pathway activation. The results suggested that geniposide could be a potential candidate drug for treatment of vascular damage in SSc patients.