Dataset Information

DARTS-MS chemoproteomic profiling of ginkgolide J-associated protease-susceptibility candidate proteins in rat PASMC lysates

ABSTRACT: This dataset contains DIA-MS raw files and processed DIA-NN results from a DARTS-MS chemoproteomic experiment designed to identify ginkgolide J-associated protease-susceptibility candidate proteins in primary rat pulmonary artery smooth muscle cell (PASMC) lysates. The experiment included three groups with three biological replicates per group: DMSO vehicle control, protease-only group, and ginkgolide J plus protease group. PASMC protein lysates in the ginkgolide J plus protease group were incubated with ginkgolide J at 25 μM before limited proteolysis with Pronase E. DARTS-MS was used as a target-discovery chemoproteomic approach to detect ligand-associated changes in protease susceptibility rather than conventional steady-state protein expression changes.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Xiangyun Gai

PROVIDER: PXD078800 | iProX | Mon May 25 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

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Publications

Serum Pharmacochemistry-Guided DARTS-MS Profiling Reveals Potential Mechanisms of Caragana jubata Against Hypoxic Pulmonary Hypertension.

Hu Jiacheng J Qiao Yujie Y Lei Gaoxiang G Gai Xiangyun X Xia Qingqing Q Hu Qiuqin Q Sun Haotian H Wang Hongmai H Li Zhanqiang Z Zhao Yuefu Y Wang Jinyu J

International journal of molecular sciences 20260627 13

Hypoxic pulmonary hypertension (HPH) is a progressive vascular disease characterized by an abnormal increase in pulmonary arterial pressure resulting from pulmonary vasoconstriction and pulmonary vascular remodeling (PVR). Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are key drivers of PVR. Caragana jubata (Pall.) Poir. (C. jubata), known as "zuomaoxing" in Tibetan medicine, is traditionally used to treat blood-related disorders. However, t ...[more]

PMID: 42450088

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Project description:Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) is a potential treatment for patients suffering from aggressive multiple sclerosis (MS). However it remains unresolved whether autologous CD34+ hematopoietic progenitor cells of MS patients show gene expression differences prior to aHSCT that indicate a preset proinflammatory state, which would then also predispose to or predetermine recurrence of the autoimmune disease. To approach this key point we compared the gene expression signature of CD34+ and CD34- cells collected from MS patients and healthy donors (HD). Whole genome gene expression of CD34+ and CD34- cells was analysed with the Human 4x44K Design Array (Agilent-Technologies). As main observation we found only minor differences in the gene expression signature of MS patients compared to HD. Only a single gene, troponin-type-1 (TNNT1), reached statistical significance after correction for multiple comparisons (logFC=3.1, p<0.01). There was a decreased expression of several protease genes, myeloperoxidase (MPO), neutrophil-elastase (ELA2), cathepsin-G (CTSG) and serine-protease 21 (PRSS21) in HPCs of MS patients, albeit not reaching statistical significance. In summary we did not detect substantial alterations in the gene expression profile of CD34+ HPCs in MS. Our data support the use of autologous hematopoietic stem cell transplantation for treatment of an autoimmune disease. Samples of CD34+ cells were obtained from 4 female MS patients and 4 age matched healthy donors (3 female) mobilized by G-CSF (2x5M-NM-<g/kg/day) and 4 MS patients (2 female) mobilized by G-CSF (5M-NM-<g/kg/day) plus Cyclophosphamide (Cy, 4g/m2). White blood cells, containing the CD34+ cell fraction, were collected by leucocytapheresis from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and processed at one center and CD34+ HPCs purified by magnetic bead separation using the autoMACS system (Miltenyi). Purity and viability of CD34+ cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human 4x44K Design Array (Agilent-Technologies).

Project description:Genome-wide association studies in multiple sclerosis (MS) identified a polymorphism (rs6897932) located in the coding region of the alpha chain of the cytokine receptor interleukin 7 receptor (IL7R) as a component that increases susceptibility to develop the disease. This single nucleotide polymorphism (SNP) affects the splicing of the primary transcript leading to genotype-defined transcript ratios encoding either a full length membrane spanning form or a soluble receptor chain. Genotyping at the IL7R locus reveals that the region can be described by four haplotypes. Interestingly, only one out of three haplotypes harbouring the associated SNP is positively associated with MS whereas the other two do not show association. The minor allele containing haplotype shows a reduced susceptibility to develop MS. We hypothesized that additional functional or phenotypic differences exist between individuals homozygous for haplotypes shown to have either positive, negative, or neutral effect, on susceptibility to develop MS. Gene expression profiles of CD4+ T cells from MS individuals before and after stimulation with IL7 were recorded. Haplotype-specific gene signatures were found indicating small alterations in IL7/IL7R signal processing/sensitivity through JAK/STAT and p38/MAPK14. We can not exclude that the obtained signatures result from differences within the CD4+ T cell compartment that, in fact, should be seen as a consequence of systemic haplotype-specific processing of homeostatic and proliferation signals transmitted through IL7/IL7R. Samples of CD4+ cells were obtained from 7 MS patients (homozygous for Hap1 (3), Hap2 (2), Hap3 (2)). CD4+ cells were collected from peripheral blood, frozen and stored in liquid nitrogen. All samples were thawed and CD4+ cells were purified by magnetic bead separation. Purity and viability of cells was analyzed by Fluorescence Activated Cell Sorter (FACS). Total cellular RNA were extracted with TRIzol reagent and analyzed with the Human Gene 1.0 ST Array (affymetrix). IL7R haplotypes and susceptibility to develop MS: Hap1 homozygous <-> Risk <-> positive effect on MS susceptibility Hap2 homozygous <-> Hap2 <-> neutral effect on MS susceptibility Hap3 homozygous <-> Prot <-> neutral effect on MS susceptibility [Note: Haplotype nomenclature subject to revision.]

Dataset Information

DARTS-MS chemoproteomic profiling of ginkgolide J-associated protease-susceptibility candidate proteins in rat PASMC lysates

Publications

Serum Pharmacochemistry-Guided DARTS-MS Profiling Reveals Potential Mechanisms of <i>Caragana jubata</i> Against Hypoxic Pulmonary Hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

DARTS-MS chemoproteomic profiling of ginkgolide J-associated protease-susceptibility candidate proteins in rat PASMC lysates

Publications

Serum Pharmacochemistry-Guided DARTS-MS Profiling Reveals Potential Mechanisms of &lt;i&gt;Caragana jubata&lt;/i&gt; Against Hypoxic Pulmonary Hypertension.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Serum Pharmacochemistry-Guided DARTS-MS Profiling Reveals Potential Mechanisms of <i>Caragana jubata</i> Against Hypoxic Pulmonary Hypertension.