Involvement of PDCD5 in the regulation of apoptosis in fibroblast-like synoviocytes of rheumatoid arthritis.
Apoptosis is reduced in the synovial tissue of patients with rheumatoid arthritis (RA), possibly due to decreased expression of pro-apoptotic genes. Programmed Cell Death 5 (PDCD5) has been recently identified as a protein that mediates apoptosis. Although PDCD5 is down-regulated in many human tumors, the role of PDCD5 in RA has not been investigated. Here we report that reduced levels of PDCD5 mRNA and protein are detected in RA synovial tissue (ST) and fibroblast-like synoviocytes (FLS) than in tissue and cells from patients with osteoarthritis (OA). We also report differences in the PDCD5 expression pattern in tissues from patients with these two types of arthritis. PDCD5 showed a scattered pattern in rheumatoid synovium compared with OA, in which the protein labeling was stronger in the synovial lining layer than in the sublining. We also observed increased expression and nuclear translocation of PDCD5 in RA patient-derived FLS undergoing apoptosis. Finally, overexpression of PDCD5 led to enhanced apoptosis and activation of caspase-3 in triptolide-treated FLS. We propose that PDCD5 may be involved in the pathogenesis of RA. These data also suggest that PDCD5 may serve as a therapeutic target to enhance sensitivity to antirheumatic drug-induced apoptosis in RA.
Wang
Ning
N
Arthritis Institute, People's Hospital, Peking University, Beijing 100044, PR China.
Lu
Hou-Shan
HS
Guan
Zhen-Peng
ZP
Sun
Tie-Zheng
TZ
Chen
Ying-Yu
YY
Ruan
Guo-Rui
GR
Chen
Zhan-Kun
ZK
Jiang
Jun
J
Bai
Chu-Jie
CJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004224:Diterpenes / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010616:Phenanthrenes / Q000494:pharmacology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution; D014162:Transfection
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; D004224:Diterpenes; D004852:Epoxy Compounds; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D010616:Phenanthrenes; C001899:triptolide; C505407:CASP3 protein, human; D053148:Caspase 3