![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
ABSTRACT
SIRT1 is a NAD-dependent protein deacetylase that participates in cellular regulation. The increased migration of fibroblasts is an important phenotype in fibroblast activation. The role of SIRT1 in cell migration remains controversial as to whether SIRT1 acts as an activator or suppressor of cell migration. Therefore, we have established the role of SIRT1 in the migration of human dermal fibroblasts and explored targets of SIRT1 during dermal fibroblast migration. SIRT1 and Cyr61 were expressed in human dermal fibroblasts and the stimulation with TGF-β further induced their expression. Treatment with resveratrol (RSV), a SIRT1 agonist, or overexpression of SIRT1 also promoted the expression Cyr61 in human dermal fibroblasts, whereas the inhibition of SIRT1 activity by nicotinamide or knockdown of SIRT1 decreased the level of Cyr61, as well as TGF-β or RSV-induced Cyr61 expression. Blocking of ERK signaling by PD98509 reduced the expression of Cyr61 induced by TGF-β or RSV. TGF-β, RSV, or SIRT1 overexpression enhanced β-catenin as well as Cyr61 expression. This stimulation was reduced by the Wnt inhibitor XAV939. RSV increased migration and nicotinamide attenuated RSV-induced migration of human dermal fibroblasts. Furthermore, SIRT1 overexpression promoted cell migration, whereas blocking Cyr61 attenuated SIRT1-stimulated migration of human dermal fibroblasts. SIRT1 increased cell migration by stimulating Cyr61 expression and the ERK and Wnt/β-catenin signaling. SIRT1-induced Cyr61 activity is very important for human dermal fibroblasts migration.
Acknowledgments
We are grateful to Dr. H. Seo for providing the pcDNA3.1-Myc-SIRT1 and pcDNA3.1-Myc-Control vectors.
Funding
This work was supported by a 2015 research grant from the Jeju National University Hospital.
Declaration of interest
The authors declare that they have no competing interests.
Additional information
Funding
Notes on contributors
Eun-Jeong Kwon
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.
Eun-Jung Park
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.
Hyeran Yu
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.
Jung-Sik Huh
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.
Jinseok Kim
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.
Moonjae Cho
Among the authors, E.J. Kwon wrote the first draft of the manuscript and was responsible for the experiments. M.J. Cho, H. Yu, and E.J. Park were responsible for the analysis and the interpretation of the data. J. Kim and M.J. Cho came up with the concept, design, and drafting of the manuscript. J.S. Huh prepared and supplied primary human dermal fibroblasts.