PMID- 29456665
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 15
IP  - 3
DP  - 2018 Mar
TI  - Involvement of TWEAK and the NF-kappaB signaling pathway in lupus nephritis.
PG  - 2611-2619
LID - 10.3892/etm.2018.5711 [doi]
AB  - Previous findings have identified that tumor necrosis factor-related weak inducer 
      of apoptosis (TWEAK) is associated with lupus nephritis (LN) activity status; 
      however, the mechanism involved remains unclear. The present study aimed to 
      investigate the roles of TWEAK and the nuclear factor (NF)-kappaB signaling pathway 
      in LN. TWEAK levels in the blood and urine of patients with LN or non-LN systemic 
      lupus erythematosus were measured by ELISA and compared with those in healthy 
      controls. TWEAK expression and NF-kappaB transcriptional activity in the kidney were 
      detected by western blotting, and Ki-67 and cluster of differentiation (CD) 68 
      expression were assessed using immunofluorescence. Additionally, human mesangial 
      cells (HMCs) were cultured in vitro and divided into five groups: Normal control, 
      TWEAK stimulus group, TWEAK + TWEAK blocking antibody, TWEAK + NF-kappaB inhibitor 
      (BAY 11-7082) and TWEAK + combined (blocking antibody + BAY 11-7082). Cell cycle 
      activity and Ki-67 expression in the HMCs were evaluated using flow cytometry, 
      and cell induction of macrophage chemotaxis was determined by a Transwell assay. 
      Levels of the inflammation-associated factors interleukin (IL)-6, monocyte 
      chemotactic protein 1 (MCP-1), chemokine ligand 5 (CCL5), IL-8 and IL-10 were 
      also detected by reverse transcription-quantitative polymerase chain reaction. It 
      was observed that the urine levels of TWEAK in patients with LN were 
      significantly elevated compared with those in the other groups (P<0.05). LN 
      kidneys exhibited markedly increased cell proliferative ability, macrophage 
      infiltration, TWEAK expression and NF-kappaB transcriptional activity compared with 
      normal kidneys. Furthermore, the results indicated that treatment with 
      recombinant TWEAK notably enhanced NF-kappaB transcriptional activity and 
      significantly promoted cell proliferation and cell cycle activity (P<0.05), 
      induced macrophage chemotaxis (P<0.05), significantly increased the expression of 
      the chemotactic factors IL-6, IL-8, MCP-1 and CCL5 (P<0.05), and significantly 
      reduced anti-inflammatory cytokine IL-10 mRNA expression in HMCs (P<0.05), 
      relative to normal controls. Accordingly, blocking TWEAK function or inhibiting 
      NF-kappaB activity reversed these effects. Collectively these data indicate that 
      urine TWEAK may be considered as a novel biomarker of LN activity, and that 
      blocking TWEAK function or NF-kappaB activity may effectively alleviate glomerular 
      mesangial cell proliferation and macrophage chemotaxis.
FAU - Sun, Fang
AU  - Sun F
AD  - Department of Nephrology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. 
      China.
FAU - Teng, Jian
AU  - Teng J
AD  - Department of Nephrology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. 
      China.
FAU - Yu, Pengfei
AU  - Yu P
AD  - Department of Respiratory Medicine, Yantai Yuhuangding Hospital, Yantai, Shandong 
      264000, P.R. China.
FAU - Li, Wenshuang
AU  - Li W
AD  - Department of Internal Medicine, Laiyang Tuberculosis Prevention Institution, 
      Laiyang, Shandong 265299, P.R. China.
FAU - Chang, Jing
AU  - Chang J
AD  - Department of Nephrology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. 
      China.
FAU - Xu, Honglei
AU  - Xu H
AD  - Department of Nephrology, Yantaishan Hospital, Yantai, Shandong 264000, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20180105
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC5795405
OTO - NOTNLM
OT  - cell proliferation
OT  - chemotaxis
OT  - human glomerular mesangial cells
OT  - lupus nephritis
OT  - nuclear factor-kappaB
OT  - tumor necrosis factor-related weak inducer of apoptosis
EDAT- 2018/02/20 06:00
MHDA- 2018/02/20 06:01
PMCR- 2018/01/05
CRDT- 2018/02/20 06:00
PHST- 2016/10/27 00:00 [received]
PHST- 2017/08/28 00:00 [accepted]
PHST- 2018/02/20 06:00 [entrez]
PHST- 2018/02/20 06:00 [pubmed]
PHST- 2018/02/20 06:01 [medline]
PHST- 2018/01/05 00:00 [pmc-release]
AID - ETM-0-0-5711 [pii]
AID - 10.3892/etm.2018.5711 [doi]
PST - ppublish
SO  - Exp Ther Med. 2018 Mar;15(3):2611-2619. doi: 10.3892/etm.2018.5711. Epub 2018 Jan 
      5.