CTRP3 promotes TNF-α-induced apoptosis and barrier dysfunction in salivary epithelial cells |
| |
| Institution: | 1. Department of Oral & Maxillofacial Surgery, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, China;2. Department of Oral Pathology, Peking University School and Hospital of Stomatology, China;3. Department of Human Anatomy & Histology and Embryology, Peking University Health Science Center, China;1. Department of Endocrinology, Central Theater Command General Hospital of the Chinese People’s Liberation Army, Wuhan, 430070, Hubei, China;2. School of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, Hubei, China;1. Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran;2. Department of Clinical Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran;3. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada;4. Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;5. Department of Health Sciences, College of Public Health, East Tennessee State University, Johnson City, TN, United States;6. Quillen College of Medicine, Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, United States;7. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada;8. Sleep Disorders Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran;9. Department of Biochemistry, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran |
| |
| Abstract: | BackgroundC1q/tumour necrosis factor-related protein 3 (CTRP3) plays important roles in metabolism and inflammatory responses in various cells and tissues. However, the expression and function of CTRP3 in salivary glands have not been explored.MethodsThe expression and distribution of CTRP3 were detected by western blot, polymerase chain reaction, immunohistochemical and immunofluorescence staining. The effects of CTRP3 on tumour necrosis factor (TNF)-α-induced apoptosis and barrier dysfunction were detected by flow cytometry, western blot, co-immunoprecipitation, and measurement of transepithelial resistance and paracellular tracer flux.ResultsCTRP3 was distributed in both acinar and ductal cells of human submandibular gland (SMG) and was primarily located in the ducts of rat and mouse SMGs. TNF-α increased the apoptotic rate, elevated expression of cleaved caspase 3 and cytochrome C, and reduced B cell lymphoma-2 (Bcl-2) levels in cultured human SMG tissue and SMG-C6 cells, and CTRP3 further enhanced TNF-α-induced apoptosis response. Additionally, CTRP3 aggravated TNF-α-increased paracellular permeability. Mechanistically, CTRP3 promoted TNF-α-enhanced TNF type I receptor (TNFR1) expression, inhibited the expression of cellular Fas-associated death domain (FADD)-like interleukin-1β converting enzyme inhibitory protein (c-FLIP), and increased the recruitment of FADD with receptor-interacting protein kinase 1 and caspase 8. Moreover, CTRP3 was significantly increased in the labial gland of Sjögren's syndrome patients and in the serum and SMG of nonobese diabetic mice.ConclusionsThese findings suggest that the salivary glands are a novel source of CTRP3 synthesis and secretion. CTRP3 might promote TNF-α-induced cell apoptosis through the TNFR1-mediated complex II pathway. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
