PMID- 28497987
OWN - NLM
STAT- MEDLINE
DCOM- 20180117
LR  - 20211204
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 42
IP  - 8
DP  - 2017 Aug
TI  - Elevated Activating Transcription Factor 4 and Glucose-Regulated 78 Kda Protein 
      Levels Correlate with Inflammatory Cytokines in the Aqueous Humor and Vitreous of 
      Proliferative Diabetic Retinopathy.
PG  - 1202-1208
LID - 10.1080/02713683.2017.1297998 [doi]
AB  - PURPOSE: To determine concentrations of endoplasmic reticulum (ER) stress-related 
      factors activating transcription factor 4 (ATF4) and glucose-regulated 78 kDa 
      protein (GRP78) in vitreous and aqueous humor (AqH) of patients with 
      proliferative diabetic retinopathy (PDR) and the correlation of ATF4, GRP78 and 
      inflammatory cytokines interleukin-6(IL-6) and monocyte chemoattractant protein-1 
      (MCP-1). MATERIALS AND METHODS: AqH and vitreous samples were collected from eyes 
      of patients with PDR and idiopathic macular hole (IMH) which needed vitrectomy. 
      Protein Levels of ATF4, GRP78, and IL-6, MCP-1 in samples were evaluated using 
      enzyme-linked immunosorbent assay (ELISA). RESULTS: ELISA analysis revealed 
      significantly increased levels in both AqH and vitreous of ATF4 and GRP78 in eyes 
      affected with PDR compared to the controls (all p < 0.001). The mean 
      concentrations of IL-6, MCP-1 were also higher in both AqH and vitreous samples 
      from patients with PDR compared to those of IMH (all p < 0.001). (Independent 
      Student t-test, normality test followed with Skewness-Kurtosis Test). In 
      addition, correlations of ATF4 and GRP78 with inflammatory factors IL-6 and MCP-1 
      in subjects of patients were analyzed. No significant correlation between the AqH 
      concentrations of ATF4/IL-6 and ATF4/MCP-1 was detected in eyes of PDR patients 
      (r = 0.346, p = 0.072 and r = 0.275, p = 0.157). Significant correlations were 
      observed between AqH concentrations of GRP78/IL-6 (r = 0.724, p < 0.001), 
      GRP78/MCP-1 (r = 0.654, p < 0.001) in PDR patients. Significant correlations were 
      observed between vitreous concentrations of ATF4/IL-6 (r = 0.918, p < 0.001), 
      ATF4/MCP-1 (r = 0.921, p < 0.001), GRP78/IL-6 (r = 0.978, p < 0.001), GRP78/MCP-1 
      (r = 0.979, p < 0.001) in PDR patients. No significant correlations was observed 
      between AqH concentrations of ATF4/IL-6 (r = 0.187, p = 474), ATF4/MCP-1 (r = 
      0.240, p = 0.353), GRP78/IL-6 (r = 0.321, p = 0.209) and GRP78/MCP-1 (r = 0.169, 
      p = 0.516) in eyes of IMH patients. And also no significant correlation was 
      observed between vitreous concentrations of ATF4/IL-6 (r = 0.130, p = 0.563), 
      ATF4/MCP-1(r = 0.029, p = 0.897), GRP78/IL-6 (r = 0.078, p = 0.717), GRP78/MCP-1 
      (r = 0.005, p = 0.982) in IMH patients. (Pearson correlation coefficient 
      (two-tailed)). CONCLUSIONS: Our results demonstrated that ATF4 and GRP78 may play 
      an important role in the pathogenesis of PDR and work in concert with 
      inflammatory cytokines IL-6 and MCP-1 in pathological process. ATF4 and GRP78 may 
      be good diagnostic biomarkers and new therapeutic targets for PDR. ABBREVIATIONS: 
      ER stress, endoplasmic reticulum stress; ATF4, activating transcription factor 4; 
      GRP78, glucose-regulated 78 kDa protein; AqH, aqueous humor; PDR, proliferative 
      diabetic retinopathy; IL-6, interleukin-6; MCP-1, monocyte chemoattractant 
      protein-1; IMH, idiopathic macular hole.
FAU - Wang, Yanuo
AU  - Wang Y
AD  - a Department of Ophthalmology , Ruijin Hospital, Shanghai Jiao Tong University, 
      School of Medicine , Shanghai , China.
FAU - Gao, Sha
AU  - Gao S
AD  - a Department of Ophthalmology , Ruijin Hospital, Shanghai Jiao Tong University, 
      School of Medicine , Shanghai , China.
FAU - Zhu, Yanji
AU  - Zhu Y
AD  - a Department of Ophthalmology , Ruijin Hospital, Shanghai Jiao Tong University, 
      School of Medicine , Shanghai , China.
FAU - Shen, Xi
AU  - Shen X
AD  - a Department of Ophthalmology , Ruijin Hospital, Shanghai Jiao Tong University, 
      School of Medicine , Shanghai , China.
LA  - eng
PT  - Journal Article
DEP - 20170512
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 3.6.1.- (Adenosine Triphosphatases)
SB  - IM
MH  - Activating Transcription Factor 4/*metabolism
MH  - Adenosine Triphosphatases
MH  - Aqueous Humor/*metabolism
MH  - Biomarkers/metabolism
MH  - Cytokines/*metabolism
MH  - Diabetic Retinopathy/diagnosis/*metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Follow-Up Studies
MH  - Heat-Shock Proteins/*metabolism
MH  - Humans
MH  - Inflammation/metabolism
MH  - Male
MH  - Middle Aged
MH  - Retrospective Studies
MH  - Vitreoretinopathy, Proliferative/diagnosis/*metabolism
MH  - Vitreous Body/metabolism
OTO - NOTNLM
OT  - Activating transcription factor 4
OT  - endoplasmic reticulum stress
OT  - glucose-regulated 78 kDa protein
OT  - inflammatory cytokines
OT  - interleukin-6
OT  - monocyte chemo attractant protein-1
OT  - proliferative diabetic retinopathy
EDAT- 2017/05/13 06:00
MHDA- 2018/01/18 06:00
CRDT- 2017/05/13 06:00
PHST- 2017/05/13 06:00 [pubmed]
PHST- 2018/01/18 06:00 [medline]
PHST- 2017/05/13 06:00 [entrez]
AID - 10.1080/02713683.2017.1297998 [doi]
PST - ppublish
SO  - Curr Eye Res. 2017 Aug;42(8):1202-1208. doi: 10.1080/02713683.2017.1297998. Epub 
      2017 May 12.