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Cited by 10Liver Disease Diagnosis and TreatmentLiver physiology and pathologyDrug-Induced Hepatotoxicity and Protection

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Therapeutic effects of myocardin-related transcription factor A (MRTF-A) knockout on experimental mice with nonalcoholic steatohepatitis induced by high-fat diet

Zhang, Lei, Li, Hua-Long, Zhang, Ding-Ding, Cui, Xiao-Chun·2021·Human & Experimental Toxicology
DOI 10.1177/09603271211002886
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Abstract

Objective To explore the effects of myocardin-related transcription factor A (MRTF-A) knockout on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD). Methods Normal-fat diet (NFD) or HFD was fed to MRTF-A-knockout (MRTF-A -/- ) and wild-type (WT) mice for 16 weeks. Liver histopathological status was observed using Hematoxylin and Eosin (HE) staining, Oil Red O staining, Sirius Red staining, and Immunohistochemical staining. The mRNA and protein levels in liver tissues were measured through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Results Compared with WT + HFD group, mice in MRTF-A -/- + HFD group were decreased in body weight, blood glucose, plasma insulin, liver TG and NAFLD activity score (NAS), with liver function recovery. Besides, compared with HFD-fed WT mice, HFD-fed MRTF-A -/- mice were improved in hepatic fibrosis, accompanied by decreased collagen content (%) and down-regulated expressions of α-SMA, COL1A2, TGFβ1 , and SMAD3 . In mice fed with HFD, the expression of MCP-1, CCR2, F4/80 and CD68 declined in liver tissues of MRTF-A -/- mice as compared with WT mice. Besides, in hepatic macrophages isolated from HFD-fed mice, the observed increased expression of TNF-α , IL-1β , MCP-1 , as well as decreased expression of CCR2. Compared with WT + HFD group, MRTF-A -/- + HFD group mice were decreased regarding NF-κB p65 in liver tissues. Conclusion MRTF-A knockout reduced macrophage infiltration, do…

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Metadata

Authors
Zhang, L., Li, H.-L., Zhang, D.-D., & Cui, X.-C.
Affiliations
  • Binzhou Medical University (CN)
  • Department of Infectious Diseases, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
Corresponding author
Cui, Xiao-Chun
ORCID
Zhang, Lei
Venue
Human & Experimental Toxicology
Publisher
SAGE Publications
Published
2021-03-29
Volume
40
Issue
10
Pages
1634-1645
ISSN
  • 0960-3271 (ISSN-L)
  • 1477-0903
DOI
10.1177/09603271211002886
OpenAlex
W3141193558
Cited by
10
References
1
Citations by year
2026: 2 · 2024: 2 · 2022: 5
FWCI
1.27
Type
journal article
Language
en
Open access
closed
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Human & Experimental Toxicology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
MRTF-A, nonalcoholic steatohepatitis, high-fat diet, liver fibrosis, hepatic macrophages, macrophage infiltration, NF-κB p65, liver inflammation, CCR2, MCP-1, TGF-β1/Smad3 signaling, COL1A2, alpha-smooth muscle actin, therapeutic target
MeSH terms
Animals, Mice, Inbred C57BL, RNA, Messenger, Trans-Activators, Mice, Knockout, Genetic Predisposition to Disease, Mice, Diet, High-Fat, Non-alcoholic Fatty Liver Disease

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