PMID- 26702616
OWN - NLM
STAT- MEDLINE
DCOM- 20160907
LR  - 20211122
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 17
DP  - 2015 Dec 23
TI  - Autophagy induction contributes to the resistance to methotrexate treatment in 
      rheumatoid arthritis fibroblast-like synovial cells through high mobility group 
      box chromosomal protein 1.
PG  - 374
LID - 10.1186/s13075-015-0892-y [doi]
LID - 374
AB  - BACKGROUND: Rheumatoid arthritis fibroblast-like synovial cells (RA-FLS) show 
      resistance to methotrexate (MTX) treatment. To better understand the mechanisms 
      of this resistance, RA-FLS and osteoarthritis fibroblast-like synovial cells 
      (OA-FLS) were isolated and exposed to MTX. We analyzed the autophagy induced by 
      MTX in vitro and its relationship to apoptosis. METHODS: Cell viability was 
      evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide 
      assay, and apoptosis was detected by flow cytometry and Western blot analysis. 
      Autophagy was determined by transmission electron microscopy as well as Western 
      blot analysis. The expression levels of Beclin-1, LC3, Akt, p-Akt, mammalian 
      target of rapamycin (mTOR), p-mTOR, high mobility group box chromosomal protein 1 
      (HMGB1), and an 85 kDa caspase cleaved fragment of poly(ADP-ribose) polymerase 
      were measured by Western blotting. RESULTS: MTX-induced apoptosis was increased 
      in OA-FLS compared with RA-FLS. However, MTX stimulated the autophagy response in 
      RA-FLS by inducing autophagosome formation, but not in OA-FLS. In RA-FLS, 
      transfection with Beclin-1 small interfering RNA inhibited autophagy and 
      increased susceptibility to MTX, which induces cell death. MTX upregulated 
      autophagy through its ability to enhance the expression of HMGB1 and Beclin-1 
      rather than through the Akt/mTOR pathway. CONCLUSIONS: Autophagy induction 
      contributes to resistance to MTX treatment in fibroblasts from patients with 
      rheumatoid arthritis.
FAU - Xu, Ke
AU  - Xu K
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. 
      santxuke1986@126.com.
FAU - Cai, Yong-song
AU  - Cai YS
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. cys3568@163.com.
FAU - Lu, She-Min
AU  - Lu SM
AD  - Department of Genetics and Molecular Biology, Xi'an Jiaotong University Health 
      Science Center, Xi'an, Shaanxi Province, China. lushemin@mail.xjtu.edu.cn.
FAU - Li, Xiao-Li
AU  - Li XL
AD  - Department of Internal Medicine, Xi'an Hong Hui Hospital, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi Province, China. 
      xili666@126.com.
FAU - Liu, Lin
AU  - Liu L
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. 
      liulin183092@163.com.
FAU - Li, Zhong
AU  - Li Z
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. 
      lizhong0607@126.com.
FAU - Liu, Hui
AU  - Liu H
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. 1q2we3@163.com.
FAU - Xu, Peng
AU  - Xu P
AD  - Department of Joint Surgery, Xi'an Hong Hui Hospital, Xi'an Jiaotong University 
      Health Science Center, Xi'an, 710054, Shaanxi Province, China. sousou369@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151223
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antirheumatic Agents)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Aged
MH  - Antirheumatic Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Autophagy/*drug effects
MH  - Blotting, Western
MH  - Cell Survival/physiology
MH  - Drug Resistance/*physiology
MH  - Female
MH  - Fibroblasts/drug effects/metabolism
MH  - Flow Cytometry
MH  - HMGB1 Protein/*biosynthesis
MH  - Humans
MH  - Male
MH  - Methotrexate/*therapeutic use
MH  - Microscopy, Electron, Transmission
MH  - Middle Aged
MH  - RNA, Small Interfering
MH  - Synovial Membrane/cytology
MH  - Transfection
PMC - PMC4718027
EDAT- 2015/12/26 06:00
MHDA- 2016/09/08 06:00
PMCR- 2015/12/23
CRDT- 2015/12/26 06:00
PHST- 2015/10/01 00:00 [received]
PHST- 2015/12/08 00:00 [accepted]
PHST- 2015/12/26 06:00 [entrez]
PHST- 2015/12/26 06:00 [pubmed]
PHST- 2016/09/08 06:00 [medline]
PHST- 2015/12/23 00:00 [pmc-release]
AID - 10.1186/s13075-015-0892-y [pii]
AID - 892 [pii]
AID - 10.1186/s13075-015-0892-y [doi]
PST - epublish
SO  - Arthritis Res Ther. 2015 Dec 23;17:374. doi: 10.1186/s13075-015-0892-y.