Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα

Bauer, Robert C.; Sasaki, Makoto; Cohen, Daniel M.; Cui, Jian; Smith, Mikhaila A; Yenilmez, Batuhan; Steger, David J.; Rader, Daniel J.

doi:10.1172/jci77095

Cited by 76 publications

(105 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Reduced Lats2 expression may increase proliferation in sebaceous glands, while reduced Stk40 may promote changes in lipid metabolism. Stk40 has similar effects on lipogenesis in the liver as its binding partner Trib1 . Both, Stk40 and Trib1 can post‐transcriptionally regulate the levels of Cebpa and Cebpb proteins and thereby can regulate adipogenic programmes.…”

Section: Discussionmentioning

confidence: 99%

The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

Luan

Shi

et al. 2017

Experimental Dermatology

View full text Add to dashboard Cite

Emerging evidence indicates that even subtle changes in the expression of key genes of signalling pathways can have profound effects. MicroRNAs (miRNAs) are masters of subtlety and generally have only mild effects on their target genes. The microRNA miR-31 is one of the major microRNAs in many cutaneous conditions associated with activated keratinocytes, such as the hyperproliferative diseases psoriasis, non-melanoma skin cancer and hair follicle growth. miR-31 is a marker of the hair growth phase, and in our miR-31 transgenic mouse model it impairs the function of keratinocytes. This leads to aberrant proliferation, apoptosis, and differentiation that results in altered hair growth, while the loss of miR-31 leads to increased hair growth. Through in vitro and in vivo studies, we have defined a set of conserved miR-31 target genes, including LATS2 and STK40, which serve as new players in the regulation of keratinocyte growth and hair follicle biology. LATS2 can regulate growth of keratinocytes and we have identified a function of STK40 that can promote the expression of key hair follicle programme regulators such as HR, DLX3 and HOXC13.

show abstract

Section: Discussionmentioning

confidence: 99%

The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

Luan

Shi

et al. 2017

Experimental Dermatology

View full text Add to dashboard Cite

show abstract

“…Trib1 plays a role in the degradation of CCAAT/enhancer binding protein α (C/EBPα), a crucial transcription factor for myeloid cell development, by recruiting it to E3 ubiquitin ligase. Liver‐specific knockout (KO) of Trib1 increases the hepatic expression of C/EBPα 10. Loss of C/EBPα expression inhibits the formation of granulocytes and leads to a concomitant increase in self‐renewal of hematopoietic stem cells.…”

mentioning

confidence: 99%

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Saijou

Enomoto

Matsuda

et al. 2018

Hepatology Communications

View full text Add to dashboard Cite

Tribbles pseudokinase 1 (Trib1) is a negative regulator of CCAAT/enhancer binding protein α (C/EBPα) and is known to induce granulopoiesis while suppressing monocyte differentiation. Loss of Trib1 was previously shown to increase the neutrophil population in the spleen but lead to M2‐like macrophage reduction. Because M2 macrophages are anti‐inflammatory and promote tissue repair by producing fibrogenic factors, we investigated liver fibrosis in Trib1‐deficient mice. Interestingly, loss of Trib1 suppressed fibrosis in the CCl4‐induced chronic liver injury model. Trib1 knockout increased neutrophils but had a minimal effect on the macrophage population in the liver. Hepatic expressions of neutrophil matrix metalloproteinases (Mmp)8 and Mmp9 were increased, but the production of fibrogenic factors, including transforming growth factor β1, was not affected by loss of Trib1. These results suggest that neutrophils are responsible for the suppression of fibrosis in Trib1‐deficient liver. Consistently, transplantation of Trib1‐deficient bone marrow cells into wild‐type mice alleviated CCl4‐induced fibrosis. Furthermore, expression of chemokine (C‐X‐C motif) ligand 1 (Cxcl1) by adeno‐associated viral vector in the normal liver recruited neutrophils and suppressed CCl4‐induced fibrosis; infusion of wild‐type neutrophils in CCl4‐treated mice also ameliorated fibrosis. Using recombinant adeno‐associated virus‐mediated expression of Mmp8 and Mmp9 alleviated liver fibrosis. Finally, neutrophil depletion by infusion of Ly6G antibody significantly enhanced CCl4‐induced fibrosis. Conclusion: While neutrophils are well known to exacerbate acute liver injury, our results demonstrate a beneficial role of neutrophils in chronic liver injury by promoting fibrolysis. (Hepatology Communications 2018;2:703‐717)

show abstract

“…The TRIB1 locus on chromosome 8 (Figure c and Table c) is intriguing because it harbors a genetic signal for all major classes of plasma lipoproteins as well as CAD. Of multiple genes and lncRNAs at this locus, strong data support TRIB1 as a causal gene via its role in hepatic lipoprotein metabolism (Bauer et al, ). Yet the strongest SNP signal lies at a distance from TRIB1 in a lncRNA rich region and recent work suggest that a lncRNA upstream of TRIB1 is involved in a reciprocal regulation of TRIB1 expression and may harbor a causal regulatory genetic signal for the plasma lipid and CAD traits by lncRNA cis‐regulation of TRIB1 expression and thus its cell specific actions (Douvris et al, ).…”

Section: Investigation Of Glgc‐ldl Association Within Cad Susceptibilmentioning

confidence: 99%

Bayesian Variable Selection for Post-Analytic Interrogation of Susceptibility Loci

2016

View full text Add to dashboard Cite

Understanding the complex interplay among protein coding genes and regulatory elements requires rigorous interrogation with analytic tools designed for discerning the relative contributions of overlapping genomic regions. To this aim, we offer a novel application of Bayesian variable selection (BVS) for classifying genomic class level associations using existing large meta-analysis summary level resources. This approach is applied using the expectation maximization variable selection (EMVS) algorithm to typed and imputed SNPs across 502 protein coding genes (PCGs) and 220 long intergenic non-coding RNAs (lncRNAs) that overlap 45 known loci for coronary artery disease (CAD) using publicly available Global Lipids Gentics Consortium (GLGC) (Teslovich et al., 2010; Willer et al., 2013) meta-analysis summary statistics for low-density lipoprotein cholesterol (LDL-C). The analysis reveals 33 PCGs and three lncRNAs across 11 loci with >50% posterior probabilities for inclusion in an additive model of association. The findings are consistent with previous reports, while providing some new insight into the architecture of LDL-cholesterol to be investigated further. As genomic taxonomies continue to evolve, additional classes such as enhancer elements and splicing regions, can easily be layered into the proposed analysis framework. Moreover, application of this approach to alternative publicly available meta-analysis resources, or more generally as a post-analytic strategy to further interrogate regions that are identified through single point analysis, is straightforward. All coding examples are implemented in R version 3.2.1 and provided as supplemental material.

show abstract

Tribbles-1 regulates hepatic lipogenesis through posttranscriptional regulation of C/EBPα

Cited by 76 publications

References 45 publications

The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

The major miR‐31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation

Neutrophils alleviate fibrosis in the CCl4‐induced mouse chronic liver injury model

Bayesian Variable Selection for Post-Analytic Interrogation of Susceptibility Loci

Contact Info

Product

Resources

About