PMID- 26303122
OWN - NLM
STAT- MEDLINE
DCOM- 20160520
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 17
IP  - 1
DP  - 2015 Aug 25
TI  - Expression of Semaphorin 4A and its potential role in rheumatoid arthritis.
PG  - 227
LID - 10.1186/s13075-015-0734-y [doi]
LID - 227
AB  - INTRODUCTION: Semaphorin 4A (Sema4A) plays critical roles in many physiological 
      and pathological processes including neuronal development, angiogenesis, immune 
      response regulation, autoimmunity, and infectious diseases. The present study 
      aimed to investigate its expression and biological activity in rheumatoid 
      arthritis (RA). METHODS: RNA and protein were isolated from synovial tissues in 
      RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A 
      (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on 
      the biological activity of synovial fibroblasts of RA (RASFs). Expression of 
      Sema4A and NF-kappaB were measured by quantitative RT-PCR (qRT-PCR) and Western blot 
      after lipopolysaccharide (LPS) stimulation. Chromatin immunoprecipitation (ChIP) 
      and siRNA targeting p50 and p60 were applied to detect the regulation of Nuclear 
      factor kappa (NF-kappaB) on Sema4A. Sema4A, interleukin 1beta (IL-1beta), interleukin 6 
      (IL-6), and tumor necrosis factor-alpha (TNF-alpha) secretion were measured by 
      ELISA-based assays. RESULTS: Increased levels of Sema4A were detected in the 
      synovial tissue and fluid of patients with RA compared with those with OA. 
      Furthermore, synovial fluid level of Sema4A correlated with Disease Activity 
      Score (DAS) in RA. Treatment with rhSema4A promoted invasion of RASFs by 
      upregulating the expression of Matrix metallopeptidase3 (MMP3), MMP9, 
      alpha-smooth muscle actin(alpha-SMA), and Vimentin, and exacerbated inflammation by 
      promoting the production of IL-6 in RASFs, as well as IL-1beta and TNF-alpha in THP-1 
      cells. The induction of IL-6 and TNF-alpha by Sema4A was confirmed at the protein 
      level in fluid samples from patients with RA. Knock-down experiments showed the 
      participation of Plexin B1 towards rhSema4A in the induction of cytokines. In 
      addition, LPS stimulation induced Sema4A expression in RASFs in an 
      NF-kappaB-dependent manner, and rhSema4A treatment could also activate NF-kappaB 
      signaling. CONCLUSIONS: These findings suggest an NF-kappaB-dependent modulation of 
      Sema4A in the immune response. Further, increased expression of Sema4A is 
      required to promote inflammation of RA.
FAU - Wang, Lin
AU  - Wang L
AD  - Research Center for Medicinal Biotechnology, Key Laboratory for Rare & Uncommon 
      Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, 
      China. wanglin.83@163.com.
FAU - Song, Guanhua
AU  - Song G
AD  - Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, China. 
      ghsong@163.com.
FAU - Zheng, Yabing
AU  - Zheng Y
AD  - Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jingshi Road 16766, Jinan, Shandong, 250014, People's Republic of 
      China. ybzheng@163.com.
FAU - Tan, Weiwei
AU  - Tan W
AD  - Department of Pathology, Shandong University Medical School, Jinan, China. 
      tanvv@163.com.
FAU - Pan, Jihong
AU  - Pan J
AD  - Research Center for Medicinal Biotechnology, Key Laboratory for Rare & Uncommon 
      Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, 
      China. jhpan@163.com.
FAU - Zhao, Yu
AU  - Zhao Y
AD  - Research Center for Medicinal Biotechnology, Key Laboratory for Rare & Uncommon 
      Diseases of Shandong Province, Shandong Academy of Medicinal Sciences, Jinan, 
      China. yzhao@163.com.
FAU - Chang, Xiaotian
AU  - Chang X
AD  - Medical Research Center of Shandong Provincial Qianfoshan Hospital, Shandong 
      University, Jingshi Road 16766, Jinan, Shandong, 250014, People's Republic of 
      China. chang_qf@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150825
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (SEMA4A protein, human)
RN  - 0 (Semaphorins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
CIN - Arthritis Res Ther. 2015;17:313. PMID: 26542940
MH  - Adult
MH  - Aged
MH  - Arthritis, Rheumatoid/*genetics/metabolism/pathology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Fibroblasts/*metabolism
MH  - Gene Expression/drug effects/*genetics
MH  - Humans
MH  - Interleukin-6/blood/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/genetics/metabolism
MH  - RNA Interference
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Semaphorins/blood/*genetics/metabolism
MH  - Severity of Illness Index
MH  - Signal Transduction/genetics
MH  - Synovial Membrane/*metabolism/pathology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/blood/metabolism
PMC - PMC4549119
EDAT- 2015/08/26 06:00
MHDA- 2016/05/21 06:00
PMCR- 2015/08/25
CRDT- 2015/08/26 06:00
PHST- 2015/04/10 00:00 [received]
PHST- 2015/07/31 00:00 [accepted]
PHST- 2015/08/26 06:00 [entrez]
PHST- 2015/08/26 06:00 [pubmed]
PHST- 2016/05/21 06:00 [medline]
PHST- 2015/08/25 00:00 [pmc-release]
AID - 10.1186/s13075-015-0734-y [pii]
AID - 734 [pii]
AID - 10.1186/s13075-015-0734-y [doi]
PST - epublish
SO  - Arthritis Res Ther. 2015 Aug 25;17(1):227. doi: 10.1186/s13075-015-0734-y.