Naringenin modulates the NO-cGMP-PKG signaling pathway through AKT binding to enhance osteogenic differentiation in hPDLSCs
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1105999 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28837409_1.fastq.gz | Fastqsanger.gz | |||
| SRR28837409_2.fastq.gz | Fastqsanger.gz | |||
| SRR28837410_1.fastq.gz | Fastqsanger.gz | |||
| SRR28837410_2.fastq.gz | Fastqsanger.gz | |||
| SRR28837411_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Naringenin (NAR) is a prominent flavanone, and it has been recognized for its capacity to promote osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in prior research. The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. In the present study, the protein-protein interaction (PPI) network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression were evaluated by PCR and western blotting. Alizarin red and alkaline phosphatase staining were employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co-localization of NAR molecular probes and AKT in cells. Repair of mandibular defects was assessed by micro computed tomography (micro-CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein AKT. The results demonstrated that activation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway promoted the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated NAR’s ability to promote the osteogenic differentiation of hPDLSCs. Micro-CT and Masson staining revealed more new bone formation at the defect site in the NAR gavage group. Immunofluorescence assays confirmed upregulated expression of Runt-related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the present study suggests that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO-cGMP-PKG signaling pathway through its binding to AKT.
2024-05-23 | GSE266150 | GEO
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development.
2024-06-24 | PXD049017 | Pride
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development
2024-06-24 | PXD048979 | Pride
Project description:The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals necessary for malaria parasite development.
2024-06-24 | PXD049083 | Pride
Project description:The inherited eye disease Retinitis Pigmentosa (RP) causes the loss of photoreceptors by a still unknown cell death mechanism. During this degeneration, cGMP levels become elevated, leading to over-activation of the cGMP-binding protein cGMP-dependent protein kinase (PKG). cGMP analogs selectively modified to have inhibitory actions on PKG have aided in impeding photoreceptor death, and one such cGMP analog is Rp-8-Br-PET-cGMPS. However, cGMP analogs have previously been shown to interact with numerous targets, so to further evaluate Rp-8-Br-PET-cGMPS’ efficacy for therapies, it is necessary to comprehend its target-selectivity and what potential cellular mechanism(s) it may affect within the photoreceptors.
2024-05-07 | PXD031693 | Pride
Project description:In malaria parasites, all cGMP-dependent signalling is mediated through a single cGMP-dependent protein kinase (PKG). A major function of PKG is to control calcium signals essential for the parasite to exit red blood cells or for transmission to the mosquito vector. However, how PKG controls these signals in the absence of known second messenger-dependent calcium channels or scaffolding proteins remains a mystery. Here we identify a tightly-associated PKG partner protein in both Plasmodium falciparum asexual blood stages and P. berghei gametocytes. Named ICM1, the partner is a polytopic membrane protein with homology to transporters and calcium channels, raising the possibility of a direct functional link between PKG and calcium homeostasis. Phosphoproteomic analyses in both Plasmodium species highlight a densely phosphorylated region of ICM1 with multiple phosphorylation events dependent upon PKG activity. Stage-specific depletion of ICM1 in P. berghei blocks gametogenesis due to the inability of mutant parasites to mobilise intracellular calcium upon PKG activation, whilst conditional disruption of P. falciparum ICM1 results in reduced cGMP-dependent calcium mobilisation associated with defective egress and invasion. Our findings provide new insights into the atypical calcium homeostasis in malaria parasites essential for pathology and disease transmission.
2021-02-10 | PXD020381 | Pride
Project description:Through transcriptomic profiling, we compared differentially expressed genes between WT and pkg mutant treated with Br-cGMP, we found that PKG as primary receptor mediated cGMP signaling in rice.
2020-08-24 | GSE119028 | GEO
Project description:Bone morphogenetic protein (BMP)9 is crucial for osteogenic differentiation. Our RNA-sequencing results revealed that calcium release-activated calcium modulator 2 (ORAI2) was upregulated in mesenchymal stem cells (MSCs) in which osteogenic differentiation was induced by BMP9. ORAI2 is a subunit of store-operated Ca2+ (SOC) channels, which is associated with the second messenger Ca2+. In this study, we found that ORAI2 was downregulated in the bone tissue of ovariectomy (OVX) rats. Subsequently, we examined the impact of ORAI2 on BMP9-induced MSC osteogenic differentiation. Exogenous ORAI2 expression promoted osteogenic differentiation in vitro and bone repair in vivo, whereas silencing ORAI2 inhibited them. Similar results were also revealed using the SOC entry inhibitor SKF96365. Mechanistically, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the effects of ORAI2 may involve the PI3K/AKT signaling pathway. Consistent with the KEGG analysis results, western blotting results further revealed that exogenous expression of ORAI2 increased the levels of phosphorylated-Akt in cells undergoing BMP9-induced osteogenic differentiation, whereas silencing of ORAI2 reduced them. Furthermore, mass spectrometry results suggested that ORAI2 may bind to IQGAP1, which was confirmed by co-immunoprecipitation and western blotting; notably, ORAI2 could interact with IQGAP1 and then facilitate mitogen-activated protein kinase/ERK1/2 signaling. Our results demonstrated that ORAI2 may promote osteogenic differentiation and play an important role in osteogenesis.
2024-08-31 | GSE253866 | GEO
Project description:cGMP is well-known secound messanger involved in vascular homeostasis. However little is known the effect of cGMP inducer on mRNA expression in cancer cells. We performed microarrays to revealed the transcriptional change of a human pancreatic ductal adenocarcinoma (PDCA) cell line (Panc -1) to cGMP inducer Bay41-2272 in order to provide insight into impact of cGMP induction on Panc-1 cells.
2016-09-01 | GSE66403 | GEO
Project description:cGMP is well-known secound messanger involved in vascular homeostasis. However little is known the effect of cGMP inducer on mRNA expression in cancer cells. We performed microarrays to revealed the transcriptional change of a human pancreatic ductal adenocarcinoma (PDCA) cell line (Panc -1) to cGMP inducer Bay41-2272 in order to provide insight into impact of cGMP induction on Panc-1 cells. Panc-1 Human PDCA cells were treated with vehicle (DMSO) or 5 μM Bay41-2272 for 48 h and total RNA was extracted by using TRIzol Reagent. The microarray analysis was conducted on the Panc-1 cells expressing by using Agilent Microarray.
2016-09-01 | E-GEOD-66403 | biostudies-arrayexpress