Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits the Viability and Invasiveness of Hypoxic Rheumatoid Arthritis Fibroblast-Like Synoviocytes via PI3K/Akt Signaling.
This study was undertaken to explore the effects of trichostatin A (TSA), an inhibitor of histone deacetylase, on the viability, apoptosis, and invasiveness of hypoxic rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). RA FLSs were exposed to hypoxia for 24 h in the presence or absence of 2 μM TSA and tested for cell viability, apoptosis, invasion, and gene expression. The involvement of the phosphatidylinositol-3-kinase (PI3K)/Akt pathway was checked. TSA significantly inhibited the viability and induced apoptosis of hypoxic RA FLSs, compared to vehicle control. TSA blocked hypoxia-induced invasion of RA FLSs during Matrigel invasion assays and reduced the expression of matrix metalloproteinases (MMP-2 and MMP-9) and PI3K and phosphorylation of Akt. Overexpression of constitutively active Akt reversed TSA-mediated suppression of invasiveness and downregulation of MMP-2 and MMP-9. Our results indicate the antisurvival and antiinvasive activities of TSA in hypoxic RA FLSs, which is associated with inactivation of PI3K/Akt signaling.
Department of Integrated Chinese and Western Medicine, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, People's Republic of China. yongzhangwuhan@163.com.
Yong
Y
Zhang
Department of Respiratory Disease, Wuhan General Hospital of Guangzhou Military Command, Wuhan, 430070, People's Republic of China.
Bo
B
Zhang
D001172:Arthritis, Rheumatoid / Q000473:pathology*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D000070918:Synoviocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
Histone Deacetylase Inhibitor; Hypoxia; Invasiveness; Rheumatoid Arthritis Fibroblast-Like Synoviocytes; Trichostatin A