Matching Items (2)

127886-Thumbnail Image.png

An integrative method to decode regulatory logics in gene transcription

Description

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

Contributors

Agent

Created

Date Created
  • 2017-10-19

128573-Thumbnail Image.png

Activation of E-prostanoid 3 receptor in macrophages facilitates cardiac healing after myocardial infarction

Description

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C[superscript low] and Ly6C[superscript high]) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E[subscript 2] is involved in the Mo/Mp-mediated inflammatory response,

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C[superscript low] and Ly6C[superscript high]) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E[subscript 2] is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C[superscript low] Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signalling and subsequently inhibits Ly6C[superscript low] Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE[subscript 2]/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6C[superscript low] Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

Contributors

Agent

Created

Date Created
  • 2017-03-03