Dataset Information

Proteomics of rat neonatal cardiac fibroblasts

ABSTRACT: Gβγ subunits are involved in many different signalling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear Gβγ, we investigated the functional role of Gβγ signalling in regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. Following activation of the angiotensin II type I receptor in these cells, Gβγ dimers interact with RNA polymerase II (RNAPII). Our findings suggest that Gβ1γ recruitment to RNAPII negatively regulates the fibrotic transcriptional response, which can be overcome by strong fibrotic stimuli. In these specific proteomics experiments, we compared the differential protein abundance in Gβ1 knockdown and WT cardiac fibroblasts following angiotensin II treatment using a bottom-up data-dependent approach.

INSTRUMENT(S): impact II

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Heart, Fibroblast

SUBMITTER: Andrew Bayne

LAB HEAD: Jean-Francois Trempe

PROVIDER: PXD025993 | Pride | 2023-05-10

REPOSITORIES: Pride

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Publications

Gβγ subunits colocalize with RNA polymerase II and regulate transcription in cardiac fibroblasts.

Khan Shahriar M SM Martin Ryan D RD Bayne Andrew A Pétrin Darlaine D Bourque Kyla K Jones-Tabah Jace J Bouazza Celia C Blaney Jacob J Lau Jenny J Martins-Cannavino Kimberly K Gora Sarah S Zhang Andy A MacKinnon Sarah S Trieu Phan P Clarke Paul B S PBS Trempe Jean-François JF Tanny Jason C JC Hébert Terence E TE

The Journal of biological chemistry 20230224 4

Gβγ subunits mediate many different signaling processes in various compartments of the cell, including the nucleus. To gain insight into the functions of nuclear Gβγ signaling, we investigated the functional role of Gβγ signaling in the regulation of GPCR-mediated gene expression in primary rat neonatal cardiac fibroblasts. We identified a novel, negative, regulatory role for the Gβ<sub>1</sub>γ dimer in the fibrotic response. Depletion of Gβ<sub>1</sub> led to derepression of the fibrotic respo ...[more]

PMID: 36841480

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Project description:In order to characterize gene expression networks linked to AT1 angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT1A receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. At baseline, 405 genes were differentially expressed (>1.5X) between WT and KO kidneys. Of these, more than 80% were up-regulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ~805 genes was altered (18% up-regulated, 82% repressed). Genes in metabolism and ion transport pathways were up-regulated while there was attenuated expression of protective genes against oxidative stress including glutathione synthetase and mitochondrial SOD2. Angiotensin II infusion has little effect on blood pressure in KOs. Nonetheless, expression of more than 250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were up-regulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation. To define gene expression patterns in kidney triggered by of activation AT1 receptors, we used genome-wide transcriptional analysis of RNA from kidneys of wild-type and AT1A receptor-deficient mice at baseline and after 2 days of angiotensin II infusion (1 ug/kg/min), using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays. All of the experiments were conducted with male mice 2.5 months old and included 3 mice per experimental group. Synthesis of cRNA, hybridization and scanning of chips were conducted by Duke University microarray core facility (Duke University, Durham, NC).

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