PMID- 24452638
OWN - NLM
STAT- MEDLINE
DCOM- 20140615
LR  - 20211203
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 306
IP  - 8
DP  - 2014 Apr 15
TI  - ER stress triggers MCP-1 expression through SET7/9-induced histone methylation in 
      the kidneys of db/db mice.
PG  - F916-25
LID - 10.1152/ajprenal.00697.2012 [doi]
AB  - Epigenetics plays a key role in the pathogenesis of diabetic nephropathy (DN), 
      although the precise regulatory mechanism is still unclear. Here, we examined the 
      role of endoplasmic reticulum (ER) stress in histone H3 lysine 4 (H3K4) 
      methyltransferase SET7/9-induced monocyte chemoattractant protein-1 (MCP-1) 
      expression in the kidneys of db/db mice. Our results indicate that the expression 
      of MCP-1 significantly increased in the kidneys of db/db mice in a time-dependent 
      manner. An increased chromatin mark associated with an active gene (H3K4me1) at 
      MCP-1 promoters accompanied this change in expression. The expression of SET7/9 
      and the recruitment to these promoters were also elevated. SET7/9 gene silencing 
      with small interfering (si) RNAs significantly attenuated the expression of 
      H3K4me1 and MCP-1. Furthermore, expression of signaling regulator 
      glucose-regulated protein 78 (GRP78), a monitor of ER stress, significantly 
      increased in the kidneys of db/db mice. The expression of spliced X-box binding 
      protein 1 (XBP1s), an ER stress-inducible transcription factor, and recruitment 
      to the SET7/9 promoters were also increased. XBP1s gene silencing with siRNAs 
      significantly attenuated the expression of SET7/9, H3K4me1, and MCP-1. The 
      chaperone betaine not only effectively downregulated the GRP78 and XBP1s 
      expression levels but also markedly decreased the SET7/9, H3K4me1, and MCP-1 
      levels. Luciferase reporter assay demonstrated that XBP1s participated in ER 
      stress-induced SET7/9 transcription, Taken together, these results reveal that ER 
      stress can trigger the expression of MCP-1, in part through the XBP1s-mediated 
      induction of SET7/9.
FAU - Chen, Jigang
AU  - Chen J
AD  - Dept. of Dept. of Nephrology, Xinqiao Hospital, The Third Military Medical Univ., 
      183 Xinqiao Main St., Shapingba District, Chongqing, People's Republic of China. 
      fxb12@aliyun.com.
FAU - Guo, Yanhong
AU  - Guo Y
FAU - Zeng, Wei
AU  - Zeng W
FAU - Huang, Li
AU  - Huang L
FAU - Pang, Qi
AU  - Pang Q
FAU - Nie, Ling
AU  - Nie L
FAU - Mu, Jiao
AU  - Mu J
FAU - Yuan, Fahuan
AU  - Yuan F
FAU - Feng, Bing
AU  - Feng B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140122
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (Xbp1 protein, mouse)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/*biosynthesis/urine
MH  - DNA-Binding Proteins/biosynthesis
MH  - Diabetic Nephropathies/genetics/pathology/*physiopathology
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*physiology
MH  - Heat-Shock Proteins
MH  - Histone-Lysine N-Methyltransferase/*metabolism
MH  - Kidney/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Regulatory Factor X Transcription Factors
MH  - Transcription Factors/biosynthesis
MH  - X-Box Binding Protein 1
OTO - NOTNLM
OT  - ER stress
OT  - MCP-1
OT  - diabetic nephropathy
OT  - epigenetics
EDAT- 2014/01/24 06:00
MHDA- 2014/06/16 06:00
CRDT- 2014/01/24 06:00
PHST- 2014/01/24 06:00 [entrez]
PHST- 2014/01/24 06:00 [pubmed]
PHST- 2014/06/16 06:00 [medline]
AID - ajprenal.00697.2012 [pii]
AID - 10.1152/ajprenal.00697.2012 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2014 Apr 15;306(8):F916-25. doi: 
      10.1152/ajprenal.00697.2012. Epub 2014 Jan 22.