Summary of Study ST002805
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001752. The data can be accessed directly via it's Project DOI: 10.21228/M87Q7Z This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002805 |
| Study Title | IL-1β-mediated adaptive re-programming of endogenous human cardiac fibroblasts to cells with immune features during fibrotic remodeling |
| Study Summary | The source and roles of fibroblasts and CD4 helper T-cells during maladaptive remodeling and myocardial fibrosis in pulmonary arterial hypertension (PAH) have been long debated. We demonstrate, using single-cell mass cytometry, a sub-population of endogenous human cardiac fibroblasts expressing increased levels of CD4, a helper T-cell marker, in addition to myofibroblast markers distributed in human fibrotic RV tissue, interstitial/perivascular lesions of SUGEN/Hypoxia (SuHx) rats and fibroblasts labelled with pdgfrα CreERt2/+ in R26R-tdTomato mice. Recombinant IL-1β increases IL-1R, CCR2 receptor expression, modifies the secretome, and differentiates cardiac fibroblasts to form CD68 positive cell clusters. IL-1β also activates stemness markers such as NANOG and SOX2 and genes involved in de-differentiation, lymphoid cell function and metabolic reprogramming. IL-1β induction of lineage traced primary mouse cardiac fibroblasts causes these cells to lose their fibroblast identity and acquire an immune phenotype. Our results identify IL-1β induced immune-competency in human cardiac fibroblasts and suggest that fibroblast secretome modulation may constitute a therapeutic approach to PAH and other diseases typified by inflammation and fibrotic remodeling. |
| Institute | Brown University |
| Department | Molecular Pharmacology, Physiology and Biotechnology |
| Laboratory | Siamwala Lab |
| Last Name | Siamwala |
| First Name | Jamila |
| Address | 830 Chalkstone Avenue, Building 35 |
| jamila_siamwala@brown.edu | |
| Phone | 6192136223 |
| Submit Date | 2023-07-18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | Other |
| Release Date | 2023-08-07 |
| Release Version | 1 |
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Treatment:
| Treatment ID: | TR002921 |
| Treatment Summary: | hVCF (2 x 106) were seeded and grown to confluence and treated with IL-1β (10 ng/ml) for 24h. Conditioned media (1ml) from the vehicle or IL-1β treated hVCF cells were used for the metabolomics analysis. |
