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Thrombopoietin mimetic reduces mouse lung inflammation and fibrosis after radiation by attenuating activated endothelial phenotypes

ABSTRACT: Thrombopoietin mimetic reduces mouse lung inflammation and fibrosis after radiation by attenuating activated endothelial phenotypes

PROVIDER: PRJNA1140648 | ENA |

REPOSITORIES: ENA

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Thrombopoietin mimetic reduces mouse lung inflammation and fibrosis after radiation by attenuating activated endothelial phenotypes

Project description:Radiation-induced lung injury (RILI) initiates radiation pneumonitis and progresses to fibrosis as the main side effect of lung cancer patients treated with radiotherapy. There is no effective drug for RILI. Sustained vascular activation is a major contributor to the establishment of chronic disease. Here, using a whole thoracic irradiation (WTI) mouse model, we investigated the mechanisms and effectiveness of thrombopoietin mimetic (TPOm) for preventing RILI. We demonstrated that administering TPOm 24 hours before irradiation decreased histologic lung injury score, apoptosis, vascular permeability, expression of pro-inflammatory cytokines, and neutrophil infiltration in the lung of mice 2 weeks after WTI. We described the expression of c-MPL, a TPO receptor, in mouse primary pulmonary microvascular endothelial cells, showing TPOm reduced endothelial cell-neutrophil adhesion by inhibiting ICAM-1 expression. Seven months after WTI, TPOm-treated lung exhibited less collagen deposition, expression of MMP-9, TIMP-1, IL-6, TGF-b, and p21. Moreover, TPOm improved lung vascular structure, lung density, and respiration rate, leading to a prolonged survival time after WTI. Single-cell RNA sequencing analysis of lungs 2 weeks after WTI revealed that TPOm shifted populations of capillary endothelial cells towards a less activated and more homeostatic phenotype. Taken together, TPOm is protective for RILI by inhibiting endothelial cell activation.

2024-08-01 | GSE273235 | GEO

Notch1 regulates hepatic thrombopoietin production

Project description:Notch1 regulates hepatic thrombopoietin production

| PRJNA1054472 | ENA

FXR Agonism with Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden

Project description:FXR Agonism with Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden

| PRJNA1096356 | ENA

thrombopoietin-induced megakaryocyte differentiation with and without nicotinamide

2006-08-25 | GSE4974 | GEO

Expression data from iPSC-derived mimetic Vγ9Vδ2 T cells and mimetic NK cells

Project description:We designed and demonstrated a synthetic strategy to derive mimetic Vγ9Vδ2 T cells endowed with NKRs from iPSCs. We used microarrays to compare mRNA expression profiles of such iPSC-derived mimetic Vγ9Vδ2 T cells with other peripheral blood lymphocytes.

2019-05-31 | GSE126035 | GEO

Expression data from iPSC-derived mimetic Vγ9Vδ2 T cells and mimetic NK cells

Project description:Expression data from iPSC-derived mimetic Vγ9Vδ2 T cells and mimetic NK cells

| PRJNA520837 | ENA

Transcription of human thrombopoietin-induced megakaryocyte differentiation with and without nicotinamide vs. Universal reference sample

Project description:Culture of hematopoietic stem and progenitor cells in the presence of thrombopoietin induces megakaryocytic differentiation. Addition of nicotinamide to thrombopoietin-stimulated cultures results in significant increases in megkaryocytic differentiation including greater polyploidization and enhanced proplatelet formation. This study focuses on understanding the differences in the temporal gene expression pattern during differentiation with and without nicotinamide. Nicotinamide was added on day 5. Experiment Overall Design: Two biological experiments were analyzed. For each experiment, a sample was taken on day 5, before nicotinamide addition, and on days 6, 8, and 10 from both nicotinamide and control treated cultures. Each sample was analyzed in duplicate for a total of 14 hybridizations per culture or 28 total hybridizations.

2009-04-08 | E-GEOD-4974 | biostudies-arrayexpress

A Novel Peptide Thrombopoietin Mimetic Designing and Optimization Using Computational Approach.

Project description:Thrombopoietin receptor (TPOR) is a cytokine receptor protein present on the cell surface. The activation of TPOR by thrombopoietin (TPO) (a glycoprotein hormone) triggers an intracellular cascade of megakaryocytopoiesis for the formation of platelets. Recent studies on ex vivo megakaryocytopoiesis have evolved the possibilities of therapeutics uses. These findings have paved the way for the development of various TPO alternatives (recombinant TPO, peptide, and non-peptide TPO mimetics), which are useful in regenerative medicine. However, these alternatives possess various limitations such as induction of autoimmune effects, high production cost, low specificity, and hence activity. In the present study, a novel peptidic TPO mimetic was designed through computational studies by studying the binding sites of TPO and TMP to TPOR and analogs of known mimetics. Screening of combinatorial library was done through molecular docking using ClusPro. These studies indicated mimetic-9 as a significant molecule since it was found to have better binding score of -938.8 kcal/mol with seven hydrogen bonds and a high number of hydrophobic interactions, than known mimetic TMP with docking score of -798.4 kcal/mol and TMP dimer with docking score of -811.9 kcal/mol for TPOR. Mimetic9-TPOR complex was further assessed by the molecular dynamics simulation, and their complex was found to be stable with an RMSD value of 0.091 Å. While studying the parameters, mimetic-9 was found to have overall good physiochemical properties with positive grand average hydropathy (GRAVY) score and high instability index score and was found to be localized in the extracellular region. The designed mimetic-9 might prove to be a useful lead molecule for mimicking the role of TPO for in vitro platelet production with higher efficiency.

| S-EPMC5006622 | biostudies-literature

Prophylactic administration of recombinant human thrombopoietin in the secondary prevention of thrombocytopenia induced by XELOX adjuvant chemotherapy in patients with stage III colorectal cancer

Project description:Interventions: Case series:Preventive use of recombinant human thrombopoietin Primary outcome(s): platelet count Study Design: Single arm

| 2700221 | ecrin-mdr-crc

Thymic mimetic cells function beyond self-tolerance [mimetics]

Project description:To examine the transcriptome of various mimetic thymic epithelial cell populations (CilTEC, MyoTEC, Hetero-post TEC, microfold TEC, endocrine TEC and corneoTEC) we sorted these populations from young WT mice and performed bulk RNAseq

2023-08-28 | GSE236070 | GEO

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