ArticleMolecular and cellular biology2015
LIM-only protein FHL2 is a positive regulator of liver X receptors in smooth muscle cells involved in lipid homeostasis.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Transcription factor E4F1 as a regulator of cell life and disease progression.Science advances · 2023Review
- Comprehensive pan-cancer analysis identifies FHL2 associated with poor prognosis in lung adenocarcinoma.Translational cancer research · 2023Article
- Single-cell RNA sequencing reveals the developmental program underlying proximal-distal patterning of the human lung at the embryonic stage.Cell research · 2023Article
- Molecular Mechanisms Underlying the Progression of Aortic Valve Stenosis: Bioinformatic Analysis of Signal Pathways and Hub Genes.International journal of molecular sciences · 2023Article
- Imaging the TGFβ type I receptor in pulmonary arterial hypertension.EJNMMI research · 2023Article
- Glucose-mediated insulin secretion is improved in FHL2-deficient mice and elevated FHL2 expression in humans is associated with type 2 diabetes.Diabetologia · 2022Article
- How (Epi)Genetic Regulation of the LIM-Domain Protein FHL2 Impacts Multifactorial Disease.Cells · 2021Review
- Untangling the Cooperative Role of Nuclear Receptors in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2021Review
- Volume Load-Induced Right Ventricular Failure in Rats Is Not Associated With Myocardial Fibrosis.Frontiers in physiology · 2021Article
- LIM-only protein FHL2 attenuates vascular tissue factor activity, inhibits thrombus formation in mice andHaematologica · 2020Article
- Four-And-A-Half LIM-Domain Protein 2 (FHL2) Deficiency Aggravates Cholestatic Liver Injury.Cells · 2020Article
- An emerging link between LIM domain proteins and nuclear receptors.Cellular and molecular life sciences : CMLS · 2018Review
- Review
- 6-Mercaptopurine reduces cytokine and Muc5ac expression involving inhibition of NFκB activation in airway epithelial cells.Respiratory research · 2015Article
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The LIM-only protein FHL2 is expressed in smooth muscle cells (SMCs) and inhibits SMC-rich-lesion formation. To further elucidate the role of FHL2 in SMCs, we compared the transcriptomes of SMCs derived from wild-type (WT) and FHL2 knockout (KO) mice. This revealed that in addition to the previously recognized involvement of FHL2 in SMC proliferation, the cholesterol synthesis and liver X receptor (LXR) pathways are altered in the absence of FHL2. Using coimmunoprecipitation experiments, we found that FHL2 interacts with the two LXR isoforms, LXRα and LXRβ. Furthermore, FHL2 strongly enhances transcriptional activity of LXR element (LXRE)-containing reporter constructs. Chromatin immunoprecipitation (ChIP) experiments on the ABCG1 promoter revealed that FHL2 enhances the association of LXRβ with DNA. In line with these observations, we observed reduced basal transcriptional LXR activity in FHL2-KO SMCs compared to WT SMCs. This was also reflected in reduced expression of LXR target genes in intact aorta and aortic SMCs of FHL2-KO mice. Functionally, the absence of FHL2 resulted in attenuated cholesterol efflux to both ApoA-1 and high-density lipoprotein (HDL), in agreement with reduced LXR signaling. Collectively, our findings demonstrate that FHL2 is a transcriptional coactivator of LXRs and points toward FHL2 being an important determinant of cholesterol metabolism in SMCs.
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