Activation of Wnt signaling reduces high-glucose mediated damages on skin fibroblast cells | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 14، دوره 20، شماره 8، آبان 2017، صفحه 944-950 اصل مقاله (1.08 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.9118 | ||
| نویسندگان | ||
| Youpei Wang1؛ Xiang Zheng2؛ Qing Wang3؛ Meiqin Zheng1؛ Lingxia Pang* 3 | ||
| 1Clinical Examination Center, The Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, China 325000 | ||
| 2Emergency department of children, The Second Affiliated Hospital and Yuying children’s Hospital of Wenzhou Medical University, Wenzhou, China 325000 | ||
| 3Function Experiment Teaching Center, Wenzhou Medical University, Wenzhou, China 325305 | ||
| چکیده | ||
| Objective(s): High-glucose (HG) stress, a mimic of diabetes mellitus (DM) in culture cells, alters expression of a large number of genes including Wnt and NF-κB signaling-related genes; however, the role of Wnt signaling during HG-mediated fibroblast damage and the relationship between Wnt and NF-κB signaling have not been understood. In this study, we aimed to investigate the ffects of Wnt signaling on HG-mediated damages. Materials and Methods: Wnt3a was treated to HG-stressed human primary foreskin fibroblasts and the levels of Wnt signaling markers and cell proliferation were monitored. In addition, Wnt3a and NF-κB signaling inhibitor were assisted to analyze the relationship between two pathways. Results: The results indicated that HG treatment repressed β-catenin level, and Wnt3a treatment increased the levels of β-catenin and FZD8 as well as cell proliferation. RNA-seq based transcriptome analysis identified 207 up-regulated and 200 down-regulated genes upon Wnt3a supply. These altered genes are distributed into 20 different pathways. In addition, gene ontology (GO) analysis indicates that 20 GO terms are enriched. Wnt signaling genes were further verified by qRT-PCR and the results were similar with RNA-seq assay. Since NF-κB signaling negatively regulates Wnt marker gene expression, Bay117082, a typical NF-κB signaling inhibitor and Wnt3a were supplemented for testing β-catenin and phosphorylated IκBα (p-IκBα), respectively. Conclusion: HG positively inhibits Wnt signaling, and signaling activation via supplementation of Wnt3a rescued the defect caused by HG. NF-κB signaling negatively regulates accumulation of β-catenin, but Wnt signaling has no effects on IκBα activation. | ||
| کلیدواژهها | ||
| Damage؛ Fibroblasts؛ High-glucose؛ RNA-Seq؛ Skin؛ Wnt signaling | ||
| مراجع | ||
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1. Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med 2006; 12:62-66.
2. Braiman-Wiksman L, Solomonik I, Spira R, Tennenbaum T. Novel insights into wound healing sequence of events. Toxicol Pathol 2007; 35:767-779.
3. Brem H, Tomic-Canic M. Cellular and molecular basis of wound healing in diabetes. J Clin Invest 2007; 117:1219-1222.
4. Martin P. Wound healing--aiming for perfect skin regeneration. Science 1997; 276:75‑81.
5. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 2006; 114:597-605.
6. Obayashi K, Akamatsu H, Okano Y, Matsunaga K, Masaki H. Exogenous nitric oxide enhances the synthesis of type I collagen and heat shock protein 47 by normal human dermal fibroblasts. J Dermatol Sci 2006; 41:121-126.
7. Loots MA, Lamme EN, Mekkes JR, Bos JD, Middelkoop E. Cultured fibroblasts from chronic diabetic wounds on the lower extremity (non-insulin-dependent diabetes mellitus) show disturbed proliferation. Arch Dermatol Res 1999; 291:93-99.
8. Rowe DW, Starman BJ, Fujimoto WY, Williams RH. Abnormalities in proliferation and protein synthesis in skin fibroblast cultures from patients with diabetes mellitus. Diabetes 1977; 26:284-290.
9. Xuan YH, Huang BB, Tian HS, Chi LS, Duan YM, Wang X, et al. High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PloS One 2014; 9:e108182.
10. Pang L, Wang Y, Zheng M, Wang Q, Lin H, Zhang L, et al. Transcriptomic study of high‑glucose effects on human skin fibroblast cells. Mol Med Rep 2016; 13:2627-2634.
11. Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R, et al. The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proc Natl Acad Sci U S A 1999; 96:5522-5527.
12. Moon RT, Kohn AD, De Ferrari GV, Kaykas A. WNT and β-catenin signalling: diseases and therapies. Nat Rev Genet 2004; 5:691-701.
13. Clevers H. Wnt/β-catenin signaling in development and disease. Cell 2006; 127:469-480.
14. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 2007; 317:807-810.
15. Gordon MD, Nusse R. Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J Biol Chem 2006; 281:22429-22433.
16. Aberle H, Bauer A, Stappert J, Kispert A, Kemler R. β-catenin is a target for the ubiquitin-proteasome pathway. EMBO J 1997; 16:3797-3804.
17. Gene ontology Consortium. The gene ontology (GO) project in 2006. Nucleic Acids Res 2006; 34:D322-D326.
18. Dupuy D, Bertin N, Hidalgo CA, Venkatesan K, Tu D, Lee D, et al. Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans. Nat Biotechnol 2007; 25:663-668.
19. Dunnick J, Brix A, Cunny H, Vallant M, Shockley K. Characterization of polybrominated diphenyl ether toxicity in Wistar Han rats and use of liver microarray data for predicting disease susceptibilities. Toxicol Pathol 2012; 40:93-106. 20. Ogata H, Goto S, Sato K, Fujibuchi W, Bono H, Kanehisa M. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 1999; 27:29-34.
21. Lamers ML, Almeida ME, Vicente-Manzanares M, Horwitz AF, Santos MF. High glucose-mediated oxidative stress impairs cell migration. PloS One 2011; 6:e22865. | ||
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