PMID- 30746746
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 7
DP  - 2019 Jul
TI  - Cell-specific elevation of Runx2 promotes hepatic infiltration of macrophages by 
      upregulating MCP-1 in high-fat diet-induced mice NAFLD.
PG  - 11761-11774
LID - 10.1002/jcb.28456 [doi]
AB  - OBJECTIVE: We have demonstrated runt-related transcription factor 2 (Runx2) plays 
      important role in atherosclerosis. It has been indicated that atherosclerosis 
      shares the similar histopathology with nonalcoholic steatohepatitis (NASH), a 
      progressive stage of nonalcoholic fatty liver disease (NAFLD), on macrophages 
      infiltration. However, the function of Runx2 in NAFLD is completely unknown. 
      Here, we investigated the underlying mechanism of Runx2 triggering macrophages 
      infiltration in the development of NAFLD. METHODS: Mice were fed with high-fat 
      diet (HFD) for a long time. Histopathologic features, macrophages infiltration, 
      expression of monocyte chemotactic protein 1 (MCP-1), and Runx2 were, 
      respectively, analyzed in vivo. Lentivirus or short interfering RNA were 
      transfected in murine hepatic stellate cells (HSCs) and the transwell assay was 
      performed to verify the contribution of Runx2 for macrophages migration in vitro. 
      RESULTS: Long-term treatment with HFD induced the progression of NAFLD, and NASH 
      was initiated from 8 months on diet. HFD increased the expression of F4/80 upon 
      HFD feeding, indicated HFD promotes hepatic infiltration of macrophages in NAFLD. 
      In addition, HFD upregulated the expression of MCP-1 and Runx2 during NAFLD 
      development. Unexpectedly, Runx2 upregulation is cell-type depended in NAFLD, and 
      only abundantly elevated in activated HSCs. Furthermore, we found that Runx2 
      could increase or decrease the expression of MCP-1 in HSCs, and regulate 
      macrophages migration by influencing MCP-1 production in vitro. CONCLUSIONS: Our 
      results give evidence that the upregulation of Runx2 specific in activated HSCs 
      promotes hepatic infiltration of macrophages by increasing MCP-1 expression in 
      NAFLD, which reveals a novel mechanism and provides a cell-specific therapeutic 
      target for NAFLD.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Zhong, Li
AU  - Zhong L
AUID- ORCID: 0000-0001-8142-5702
AD  - Department of Gastroenterology, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
AD  - Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing, China.
FAU - Huang, Lu
AU  - Huang L
AD  - Chongqing Key Laboratory of Child Infection and Immunity, Children's Hospital of 
      Chongqing Medical University, Chongqing, China.
AD  - Department of Pediatric Research Institute, Children's Hospital of Chongqing 
      Medical University, Chongqing, China.
AD  - Ministry of Education Key Laboratory of Child Development and Disorders, 
      Children's Hospital of Chongqing Medical University, Chongqing, China.
FAU - Xue, Qian
AU  - Xue Q
AD  - Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical 
      University, Chongqing, China.
FAU - Liu, Chang
AU  - Liu C
AD  - Department of Critical Care Medicine, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Xu, Keshu
AU  - Xu K
AD  - Department of Gastroenterology, Union Hospital, Tongji Medical Collage, Huazhong 
      University of Science and Technology, Wuhan, China.
FAU - Shen, Wei
AU  - Shen W
AD  - Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of 
      Chongqing Medical University, Chongqing, China.
FAU - Deng, Liang
AU  - Deng L
AD  - Department of Gastroenterology, The First Affiliated Hospital of Chongqing 
      Medical University, Chongqing, China.
LA  - eng
GR  - 81400612/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20190211
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
SB  - IM
OTO - NOTNLM
OT  - HSCs
OT  - MCP-1
OT  - NAFLD
OT  - Runx2
OT  - macrophages
EDAT- 2019/02/13 06:00
MHDA- 2019/02/13 06:01
CRDT- 2019/02/13 06:00
PHST- 2018/12/06 00:00 [revised]
PHST- 2018/09/29 00:00 [received]
PHST- 2018/12/10 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2019/02/13 06:01 [medline]
PHST- 2019/02/13 06:00 [entrez]
AID - 10.1002/jcb.28456 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Jul;120(7):11761-11774. doi: 10.1002/jcb.28456. Epub 2019 
      Feb 11.