Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Promotes Regeneration of Corneal Epithelial Cells via NR4A1 Signaling Pathway
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PROVIDER: PRJNA1226947 | ENA |
REPOSITORIES: ENA
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Project description:PACAP is a neuropeptide that promotes lacrimal fluid secretion, but its direct action on corneal injury remains to be clarified. Therefore, the effect of PACAP on corneal epithelial repair was clarified using mouse corneal wound-injury model and human corneal epithelial culture cells. PAC1-R mRNA and its immunoreactivity was detected in mouse and corneal epithelium. In corneal wound-injury model mice, PACAP eye drop significantly reduced the injured area at 12 hours, and the effect was cancelled by co-treatment with the PACAP receptor antagonist. PACAP heterozygous and PAC1-R knockout mouse delayed the corneal healing. Although surgical removal of the lacrimal gland attenuates corneal healing, PACAP eye drop on the eyes significantly recuperated corneal damage. In an in-vitro study, PACAP treatment in human corneal epithelial cells significantly decreased the injury area induced by scratching. PACAP treatment in the in-vitro human corneal epithelial cell experiments significantly reduced the area of injury and abolished the corneal repair effect due to the inhibitory effect of Ara-C on proliferation. DNA whole-genome microarray analysis suggested that the nuclear receptor NR4A1 is an important factor in corneal epithelial proliferation, and THPN, which induces nuclear export of NR4A1, suppressed PACAP-induced proliferation of human corneal epithelial cells and the repair effect of mouse corneal epithelium. These data suggest that PACAP stimulates corneal repair by corneal epithelial proliferation via PAC1-R and NR4A1 transcriptional activity. PACAP could be a good candidate as an eye-drop medication for corneal injury disease including dry eye syndrome.
2025-02-27 | GSE290267 | GEO
Project description:Investigation of transcriptional changes induced in adult primary neural stem cells when stimulated with the proliferative agent PACAP (pituitary adenylate cyclase-activating polypeptide). In addition the data was compared to results obtained from a proliferation control (stimulation with a transmembrane receptor agonist) and a differentiation control (primary neural stem cells induced to differentiate by withdrawing growth factors, adding serum and plating onto solid support).
2005-05-15 | E-MEXP-322 | biostudies-arrayexpress
Project description:Corynebacterium glutamicum GlxR suppressor mutant of adenylate cyclase (cyaB) deletion strain
| PRJEB36438 | ENA
Project description:Sweat has a critical role in human body, including thermoregulation and maintenance of skin environment and health. Hyperhidrosis and anhidrosis are caused by abnormalities in sweat secretion resulting in severe skin conditions (pruritus and erythema). Bioactive peptide, pituitary adenylate cyclase-activating polypeptide (PACAP) was isolated and identified to activate adenylate cyclase in pituitary cells. In recent years, it was reported that PACAP increases sweat secretion via PAC1R in mice and promotes the translocation of AQP5 to the cell membrane through increasing intercellular [Ca2+] via PAC1R in NCL-SG3 cells. However, the intracellular signaling mechanisms by PACAP are poorly clarified. In this study, we used PAC1R knockout (KO) mice and wild-type (WT) mice to observe changes in AQP5 localization and gene expression in sweat gland by PACAP treatment. Immunohistochemistry revealed that PACAP promotes the translocation of AQP5 to lumen side in eccrine gland via PAC1R. Furthermore, PACAP up-regulates gene expression (Ptgs2, Kcnn2, Cacna1s) involved in sweat secretion in WT mice. Further, PACAP treatment down-regulated Chrna1 gene expression in PAC1R KO mice. These genes were found to be involved in multiple pathways related to sweating. Overall our data provide a solid basis for future research initiatives to develop new therapies to treat sweating disorders.
2023-01-23 | GSE223124 | GEO
Project description:The whooping cough agent, Bordetella pertussis, subverts dendritic cell (DCs) functions through powerful immunomodulatory activities of its toxins. Here we focused on the signaling action of the adenylate cyclase toxin (CyaA) that targets myeloid cells expressing the αMβ2 integrin CD11b/CD18 (known as complement receptor 3 (CR3) or Mac-1). CyaA delivers an extremely catalytically potent adenylyl cyclase enzyme domain into the cytosol of phagocytes and disrupts their innate and adaptive immune functions through unregulated production of the key signaling molecule cAMP. Here we describe the global phosphoproteomic analysis of cAMP signaling in murine bone marrow-derived DCs exposed to CyaA. Gathered data reveal toxin-triggered alternations of phosphorylation status of proteins regulating actin cytoskeleton, chromatin remodeling, mTOR activity and IL-10 gene expression. The reported findings highlight the complexity of subversive physiological manipulation that is exerted on myeloid phagocytes by the cAMP-generating adenylate cyclase toxin of Bordetellae.
2017-11-29 | PXD004733 | Pride
Project description:The aim of this study was to evaluate changes in the transcriptome due to the lack of adenylate cyclase in light or darkness. As the cAMP pathway represents an output pathway of heterotrimeric G-protein signaling ACY1 is likely to be important for regulation of enzymes in response to different nutrient conditions. Also, a light dependent effect was found earlier.
2014-01-08 | GSE53874 | GEO
Project description:Recently, our group has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP)-induced neurite projection elongation in rat adrenal-derived pheochromocytoma cell line (PC12) is mediated via PAC1 receptor-mediated dephosphorylation of CRMP2 majorly through PI3K/AKT and MEK/ERK pathways. However, the mechanism of neuronal outgrowth by PACAP, including CRMP2 dephosphorylation, remains unclear. In our previous report, we found that GSK-3β, CDK5, and Rho/ROCK dephosphorylated CRMP2 within 3 hours after the addition of PACAP, but the early dephosphorylation of CRMP2 by PACAP remains unclear. Thus, we considered it important to identify early factors in PACAP-induced neurite projection elongation and performed omics-based transcriptomic (whole genome DNA microarray) and proteomic (TMT-labeling in conjunction with liquid chromatography-tandem mass spectrometry) analyses of gene and protein expression profiles from 5-120 minutes after PACAP addition. Results surprisingly revealed a number of key regulators involved in neurite outgrowth, including known ones. We also identified factors that may be involved in CRMP2 dephosphorylation. Cross-referencing previous research, we tried to map these molecular components onto potential pathways. The results of this comprehensive analysis may provide important new information on the molecular mechanisms of neuronal differentiation induced by PACAP.
2023-03-11 | PXD039992 | Pride
Project description:Recently, our group has shown that the pituitary adenylate cyclase-activating polypeptide (PACAP)-induced neurite projection elongation in rat adrenal-derived pheochromocytoma cell line (PC12) is mediated via PAC1 receptor-mediated dephosphorylation of CRMP2 majorly through PI3K/AKT and MEK/ERK pathways. However, the mechanism of neuronal outgrowth by PACAP, including CRMP2 dephosphorylation, remains unclear. In our previous report, we found that GSK-3β, CDK5, and Rho/ROCK dephosphorylated CRMP2 within 3 hours after the addition of PACAP, but the early dephosphorylation of CRMP2 by PACAP remains unclear. Thus, we considered it important to identify early factors in PACAP-induced neurite projection elongation and performed omics-based transcriptomic (whole genome DNA microarray) and proteomic (TMT-labeling in conjunction with liquid chromatography-tandem mass spectrometry) analyses of gene and protein expression profiles from 5-120 minutes after PACAP addition. Results surprisingly revealed a number of key regulators involved in neurite outgrowth, including known ones. We also identified factors that may be involved in CRMP2 dephosphorylation. Cross-referencing previous research, we tried to map these molecular components onto potential pathways. The results of this comprehensive analysis may provide important new information on the molecular mechanisms of neuronal differentiation induced by PACAP.
2023-01-25 | GSE223333 | GEO
Project description:New neurons are born throughout the life of mammals in germinal zones of the brain known as neurogenic niches: the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus. These niches contain a subpopulation of cells known as adult neural progenitors (aNPCs), which self-renew and give rise to new neurons and glia. aNPCs are regulated by many factors present in the niche, including the extracellular matrix (ECM). We show that the neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) affects subventricular zone-derived aNPCs by increasing their surface adhesion. Gene array and reconstitution assays indicate that this effect can be attributed to the regulation of ECM components and ECM-modifying enzymes in aNPCs by PACAP. Our work suggests that PACAP regulates a bidirectional interaction between the aNPCs and their niche: PACAP modifies ECM production and remodeling, in turn the ECM regulates progenitor cell adherence. We speculate that PACAP may in this manner help restrict adult neural progenitors to the stem cell niche in vivo, with potential significance for aNPC function in physiological and pathological states.
2017-02-01 | GSE66193 | GEO
Project description:The Bordetella adenylate cyclase toxinhemolysin (CyaA) and the α-hemolysin (HlyA) of Escherichia coli both belong to the family of cytolytic pore-forming Repeats in ToXin (RTX) cytotoxins. HlyA preferentially binds the αLβ2 integrin LFA-1 (CD11a/CD18) of leukocytes and can promiscuously bind and permeabilize also a variety of other cells. CyaA bears an Nterminal adenylyl cyclase enzyme (AC) domain linked to a pore-forming RTX cytolysin (Hly) moiety and binds the complement receptor 3 (CR3, αMβ2, CD11b/CD18 or Mac-1) of myeloid phagocytes, penetrates their plasma membrane and delivers into cytosol the AC enzyme. We constructed a set of CyaA/HlyA chimeras and show that the CyaC-acylated segment and the CR3-binding RTX domain of CyaA can be functionally replaced by the much shorter HlyCacylated and LFA-1-binding RTX moiety of HlyA. Instead of binding CR3, a CyaA1710/HlyA411-1024 chimera bound the LFA-1 receptor and effectively delivered the AC enzyme into Jurkat lymphoblastoma T cells. At high chimera concentrations (25 nM), the interaction with LFA-1 was not required for CyaA1-710/HlyA411-1024 binding to CHO cells. However, interaction with the LFA-1 receptor strongly enhanced the specific capacity of the bound CyaA1-710/HlyA411-1024 chimera to penetrate cells and deliver the AC enzyme into their cytosol. Hence, interaction of the acylated RTX moiety of HlyA with LFA-1 promoted a productive membrane interaction of the chimera. These results allow to delimit the residues 400 to 710 of CyaA as the 'AC translocon' sufficient for translocation of the AC enzyme polypeptide across the plasma membrane of target cells
2020-05-11 | PXD018789 | Pride