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Single-cell RNA-seq of Bronchoalveolar Lavage Fluid Immune Cells from Padi2/Padi4 Double Knock-out Mice in Pseudomonas aeruginosa Pneumonia-induced Sepsis

ABSTRACT: Sepsis-induced acute lung injury (ALI) is prevalent in septic patients and has a high mortality rate. Considering ALI’s close link to sepsis, we used a Pseudomonas aeruginosa (PA) pneumonia-induced sepsis mouse model to investigate alveolar microenvironment alterations and lung injury post-sepsis. Peptidyl arginine deiminase (PADI) 2 and PADI4 are highly expressed in immune cells, and play substantial roles in the immune response to sepsis, but their specific functions remain unclear.We employed single-cell RNA sequencing (scRNA-seq) technology to map immune cell populations in bronchoalveolar lavage fluid (BALF) cells from Wild type (WT) and Padi2 and Padi4 double knock-out (DKO)mice in PA pneumonia-induced sepsis and sham conditions.

ORGANISM(S): Mus musculus

PROVIDER: GSE274823 | GEO | 2024/11/30

REPOSITORIES: GEO

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Disrupted development and altered hormone signaling in male Padi2/Padi4 double knockout mice

Project description:Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice for a range of reproductive defects. Results from controlled breeding trials found that DKO breeding pairs appeared to take longer to have their first litter than WT controls and that DKO male weanlings weighed significantly less than their WT counterparts. Additionally, DKO males took significantly longer than WT males to reach puberty and also had lower serum testosterone levels. Furthermore, DKO males had smaller testes than WT males and also had increased rates of germ cell apoptosis. The DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

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PADI4 ChIP-chip from MCF-7 cells

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2011-03-31 | E-GEOD-18755 | biostudies-arrayexpress

PADI4 ChIP-chip from MCF-7 cells

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Peptidylarginine deiminase 2 (PADI2) is a key regulator for osteoblast differentiation and bone formation through the maintenance of citrullination-mediated RUNX2 stability

Project description:Peptidylarginine deiminase (PADI) 2 catalyzes the posttranslational conversion of peptidyl-arginine to peptidyl-citrulline, a process called citrullination. However, the exact function of PADI2 in bone development and bone homeostasis remains unknown. In this study, we found that Padi2 deficiency lead to loss of bone mass and cleidocranial dysplasia (CCD)-like phenotype with delayed calvarial ossification and clavicular hypoplasia due to impaired osteoblast differentiation. Mechanistically, Padi2 depletion drastically reduced RUNX2 protein level and PADI2 stabilized RUNX2 from ubiquitin-proteasomal degradation. Furthermore, we identified a new modification at RUNX2, citrullination of arginine and its conversion to citrulline by PADI2. PADI2 citrullinates RUNX2 via a direct physical interaction and the citrullination sites at RUNX2 by PADI2 were identified by high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Interestingly, in mouse RUNX2 isoform 1 (528 a.a), loss of R381, a citrullination site by PADI2, drastically reduced RUNX2 protein levels, indicating that the citrullination of RUNX2 by PADI2 is required for the maintenance of RUNX2 protein stability. Collectively, our study demonstrates that PADI2-mediated citrullination play key roles in bone formation and bone homeostasis. Also, CCD may result from functional defects of RUNX2 by Padi2 deficiency. These insights into the role of PADI2 in postnatal bone formation and homeostasis and CCD pathogenesis may assist in the development of new therapies for bone diseases including CCD.

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Disrupted development and altered hormone signaling in male Padi2/Padi4 double knockout mice

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