H2R signaling maintains neutrophil homeostasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA683590 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Adaptive cell invasion maintains organ homeostasis
| PRJNA713403 | ENA
Project description:H2R deficiency accelerated progression of colitis-associated colon tumors. To identify precise expression pattern of H2R in immune cells, we performed quantitative RT-PCR and revealed that H2R is highly expressed in neutrophils. In mice, H2R deficiency significantly promoted infiltration of neutrophils into both inflammation sites and colon tumors. To precisely elucidate the downstream effects of H2R activation in neutrophils, low-density (LDNs) and high-density (HDNs) neutrophils were enriched from casein-elicited peritoneal cells of wild type and H2R deficient mice, and extracted total RNA were subjected to RNA sequencing. H2R-deficient HDNs not only presented more pro-inflammatory features through NF-kB and MAPK pathways, but also significantly suppressed T cell proliferation, which is essential for cellular immunity. On the other hand, LDNs with no H2R activation displayed a more immature phenotype compared to WT LDNs, with enhanced MYC pathway downstream expressions and a reduced expression of the maturation marker TLR4.
2022-01-26 | GSE162850 | GEO
Project description:Healthy skin maintains a diverse microbiome and a potent immune system to fight off infections. In this study, we discovered that epithelium-derived antimicrobial peptides defensins activate orphan GPCRs Mrgpra2a/b on neutrophils. This signaling axis is required for effective neutrophil-mediated skin immunity and microbiome homeostasis. We generated two mutant mouse lines, Defensin conditional knockout (Def cKO, K14-cre; Def fl/fl) in which the entire Def gene cluster is conditionally deleted from keratinocytes, and Mrgpra2 double knockout (Mrgpra2 dKO). We used high-throughput RNA sequencing to evaluate the whole transcriptomes of WT and mutant animals' skin under naive condition and 24 hours post-S. aureus infection. Disruption of defensin-Mrgpra2 signaling caused reduction of a network of pro-inflammatory and antibacterial gene expression. This study demonstrates the importance of epithelial-neutrophil signaling via the defensin-Mrgpra2 axis in maintaining healthy skin ecology and promoting antibacterial host defense.
2021-10-01 | GSE178507 | GEO
Project description:The sinoatrial node (SAN) functions as pacemaker of the heart to initiate and drive rhythmic heartbeats. The Hippo signaling pathway is a fundamental pathway for heart development and regeneration. Although abnormalities of Hippo pathway are associated with cardiac arrhythmias in human patients, yet its role in the SAN is unknown. We found that Lats1/2 inactivation caused severe sinoatrial node dysfunction (SND; sick sinus syndrome). Compared to the controls, Lats1/2 CKO mutants exhibited dysregulated calcium handling and increased fibrosis in the sinoatrial node, indicating Lats1/2 function through both cell-autonomous and non-cell-autonomous mechanisms. Notably, the Lats1/2 CKO phenotype was rescued by genetic deletion of Yap and Taz in the CCS, and these rescued mice had normal sinus rhythm and reduced fibrosis of the sinoatrial node, indicating that Lats1/2 function through Yap and Taz. CUT&Tag sequencing data showed that Yap regulates genes critical for calcium homeostasis such as Ryr2 and genes encoding paracrine factors important in intercellular communication and fibrosis induction such as Tgf-β1 and Tgf-β3. Consistently, Lats1/2 CKO mutants had decreased Ryr2 expression and increased Tgf-β1 and Tgf-β3 expression compared with control mice. We reveal for the first time that the canonical Hippo-Yap pathway has a pivotal role in functional homeostasis of the sinoatrial node.
2022-11-29 | GSE202641 | GEO
Project description:An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis
| PRJNA415988 | ENA
Project description:SIRT6 maintains redox homeostasis to promote porcine oocyte maturation
| PRJNA675479 | ENA
Project description:LSD1/KDM1A Maintains Genome-wide Homeostasis of Transcriptional Enhancers
| PRJNA362885 | ENA
Project description:Mouse neutrophil maturity analysis in homeostasis, acute-inflammation and cancer
| PRJNA749728 | ENA
Project description:The mechanistic target of rapamycin mTORC1 is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTOR inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By utilizing constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in counter-current multiplication and urine concentration. Although mTORC2 partially compensated the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice, and caused pronounced apoptosis, diminished proliferation rates and delayed recovery. These findings identify mTORC1 as an essential regulator of tubular energy metabolism and as a crucial component of ischemic stress responses. Pharmacological inhibition of mTORC1 likely affects tubular homeostasis, and may be particularly deleterious if the kidney is exposed to acute injury. Furthermore, the combined inhibition of mTORC1 and mTORC2 may increase the susceptibility to renal damage. Raptor fl/fl*KspCre and Raptor fl/fl animals were sacrificed at P14 before the development of an overt functional phenotype. Kidneys were split in half and immediately snap frozen in liquid nitrogen.
2014-06-09 | E-GEOD-54417 | biostudies-arrayexpress
Project description:Oligosaccharyl transferase that maintains ER homeostasis enhances immunity via up-regulating p38 MAP kinase signaling in C. elegans
| PRJNA556044 | ENA