The Transcription Factor Paired-Related Homeobox 1 (Prrx1) Inhibits Adipogenesis by Activating Transforming Growth Factor-β (TGFβ) Signaling

Du, Baowen; Cawthorn, William P.; Geldert, Alisha; Doucette, Casey R.; Yao, Yao; Hemati, Nahid; Kampert, Sarah E.; McCoin, Colin S.; Broome, David T.; Rosen, Clifford J.; Yang, Gongshe; MacDougald, Ormond A.

doi:10.1074/jbc.m112.440370

Cited by 57 publications

(46 citation statements)

References 62 publications

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“…The mice were fed standard chow diet or HFD ad libitum from 3 to 15 weeks of age. The mice became obese on the HFD with 40% body fat compared with 18% body fat with the normal chow diet, at which point inguinal WAT was isolated for RNA purification as described (28) and subjected to RT-qPCR.…”

Section: Methodsmentioning

confidence: 99%

SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance

Liu

Sheng

Miao

et al. 2014

Journal of Biological Chemistry

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Section: Methodsmentioning

confidence: 99%

SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance

Liu

Sheng

Miao

et al. 2014

Journal of Biological Chemistry

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“…12 Mice that lack both Prrx1 and Prrx2 have profound defects in mesenchymal cell differentiation in the craniofacial region. 15 Prrx2 has been reported to be induced by TGF-β and to increase the invasiveness of multiple cancer types through epithelial-mesenchymal transition. 15 Prrx2 has been reported to be induced by TGF-β and to increase the invasiveness of multiple cancer types through epithelial-mesenchymal transition.…”

Section: Introductionmentioning

confidence: 99%

Up‐regulation of paired‐related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a

Bai

Tang

Shan

et al. 2019

J Cellular Molecular Medi

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Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired-related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha-smooth muscle actin (α-SMA). Both Prrx2 and Wnt5a gene expressions were up-regulated in mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus-mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia-induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF-β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Bai W-W, Tang Z-Y, Shan T-C, et al. Up-regulation of paired-related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a.

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“…Additionally, the DKK2 transcripts (cluster 9), a factor which inhibits canonical anti-adipogenic Wnt signaling, were expressed at very low levels in Om and were unaffected by Dex, while Dex increased DKK2 expression in Abdsc, potentially promoting hyperplasia in this depot. Although Dex downregulated the mRNA expression of key ligands that activate TGFβ receptor signaling ( INHBA and TGFβ ) and thereby inhibit adipogenesis [49, 50], they remained higher in Om compared to Abdsc adipose tissue cultured with Dex, especially at submaximal concentrations. Thus, if translated into a functional effects, these Dex-induced alterations in gene expression may mediate depot-dependent changes in hyperplastic expansion.…”

Section: Discussionmentioning

confidence: 99%

Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women

et al. 2016

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Glucocorticoids promote fat accumulation in visceral compared to subcutaneous depots, but the molecular mechanisms involved remain poorly understood. To identify long-term changes in gene expression that are differentially sensitive or responsive to glucocorticoids in these depots, paired samples of human omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues obtained from obese women during elective surgery were cultured with the glucocorticoid receptor agonist dexamethasone (Dex, 0, 1, 10, 25 and 1000 nM) for 7 days. Dex regulated 32% of the 19,741 genes on the array, while 53% differed by Depot and 2.5% exhibited a Depot*Dex concentration interaction. Gene set enrichment analysis showed Dex regulation of the expected metabolic and inflammatory pathways in both depots. Cluster analysis of the 460 transcripts that exhibited an interaction of Depot and Dex concentration revealed sets of mRNAs for which the responses to Dex differed in magnitude, sensitivity or direction between the two depots as well as mRNAs that responded to Dex only in one depot. These transcripts were also clearly depot different in fresh adipose tissue and are implicated in processes that could affect adipose tissue distribution or functions (e.g. adipogenesis, triacylglycerol synthesis and storage, insulin action). Elucidation of the mechanisms underlying the depot differences in the effect of Dex on the expression of specific genes and pathways that regulate adipose function may offer novel insights into understanding the biology of visceral adipose tissues and their links to metabolic health.

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The Transcription Factor Paired-Related Homeobox 1 (Prrx1) Inhibits Adipogenesis by Activating Transforming Growth Factor-β (TGFβ) Signaling

Cited by 57 publications

References 62 publications

SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance

SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance

Up‐regulation of paired‐related homeobox 2 promotes cardiac fibrosis in mice following myocardial infarction by targeting of Wnt5a

Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women

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