PMID- 18512785
OWN - NLM
STAT- MEDLINE
DCOM- 20080724
LR  - 20191210
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 58
IP  - 6
DP  - 2008 Jun
TI  - Amelioration of collagen-induced arthritis in rats by adenovirus-mediated PTEN 
      gene transfer.
PG  - 1650-6
LID - 10.1002/art.23517 [doi]
AB  - OBJECTIVE: The phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway is known 
      to be activated in rheumatoid arthritis (RA) synovial tissue, which impacts cell 
      growth, proliferation, survival, and migration. Phosphatase and tensin homolog 
      deleted from chromosome 10 (PTEN) functions as a negative regulator of PI 
      3-kinase signaling, thus blocking Akt activation. The aim of this study was to 
      examine the effect of PTEN gene transfer in rats with collagen-induced arthritis 
      (CIA). METHODS: Adenoviral vectors encoding human PTEN (AdPTEN) or 
      beta-galactosidase (AdLacZ) were injected intraarticularly into rats with CIA, 
      and their treatment responses were monitored by measures of clinical, 
      radiographic, and histologic changes. The expression of phosphorylated Akt, total 
      Akt, vascular endothelial growth factor (VEGF), proinflammatory cytokines, and 
      chemokines, as well as the extent of microvessel density in the ankle joints were 
      determined. RESULTS: AdPTEN treatment reduced Akt phosphorylation and decreased 
      VEGF production in human RA synovial fibroblasts. Compared with AdLacZ treatment 
      of the rats with CIA, AdPTEN treatment significantly reduced ankle circumference, 
      articular index scores, radiography scores, and histology scores, and also 
      decreased microvessel density and levels of VEGF and interleukin-1beta. 
      Furthermore, PTEN gene transfer led to down-regulation of Akt activation and 
      increased apoptosis in the ankle joints. CONCLUSION: This study is the first to 
      demonstrate the in vivo effect of intraarticular gene delivery of PTEN on 
      amelioration of arthritis symptoms in rats with CIA, which involved 
      antiangiogenic, antiproliferative, and antiinflammatory effects of PTEN via 
      inhibition of the PI 3-kinase/Akt signaling pathway. Our findings also implicate 
      the PI 3-kinase/Akt pathway as a therapeutic target for the treatment of RA or 
      other inflammatory diseases.
FAU - Wang, Chrong-Reen
AU  - Wang CR
AD  - National Cheng Kung University Medical College, Tainan, Taiwan.
FAU - Shiau, Ai-Li
AU  - Shiau AL
FAU - Chen, Shih-Yao
AU  - Chen SY
FAU - Lin, Ling-Ling
AU  - Lin LL
FAU - Tai, Ming-Hong
AU  - Tai MH
FAU - Shieh, Gia-Shing
AU  - Shieh GS
FAU - Lin, Pey-Ru
AU  - Lin PR
FAU - Yo, Yi-Te
AU  - Yo YT
FAU - Lee, Che-Hsin
AU  - Lee CH
FAU - Kuo, Shiao-Mei
AU  - Kuo SM
FAU - Liu, Ming-Fei
AU  - Liu MF
FAU - Jou, I-Ming
AU  - Jou IM
FAU - Yang, Chyun-Yu
AU  - Yang CY
FAU - Shen, Po-Chuan
AU  - Shen PC
FAU - Lee, Hwei-Ling
AU  - Lee HL
FAU - Wu, Chao-Liang
AU  - Wu CL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Ankle Joint/pathology
MH  - Arthritis, Experimental/pathology/*therapy
MH  - Cells, Cultured
MH  - Fibroblasts/*metabolism
MH  - Gene Transfer, Horizontal
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors
MH  - Humans
MH  - PTEN Phosphohydrolase/*genetics
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/antagonists & inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
EDAT- 2008/06/03 09:00
MHDA- 2008/07/25 09:00
CRDT- 2008/06/03 09:00
PHST- 2008/06/03 09:00 [pubmed]
PHST- 2008/07/25 09:00 [medline]
PHST- 2008/06/03 09:00 [entrez]
AID - 10.1002/art.23517 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2008 Jun;58(6):1650-6. doi: 10.1002/art.23517.