Spatially resolved atlas of IPF fibroblastic foci identifies that PAK2 kinase activation is involved in fibrogenesis
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PROVIDER: PRJNA1202105 | ENA |
REPOSITORIES: ENA
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Project description:Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive fibrosis of the lung parenchyma. To identify potential therapeutic targets for IPF, we conducted spatial transcriptomic analysis and single-cell RNA sequencing (scRNA-seq). Our findings reveal that PAK plays a critical role in the immature fibroblast niche during fibrogenesis, highlighting its potential as a therapeutic target for the treatment of IPF.
2025-08-11 | GSE285246 | GEO
Project description:To further understand the pathologic microenvironment in IPF, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish normal and IPF lung in normal-looking, fibrotic foci and hyperplastic areas of IPF lung. Four IPF lungs were dissected into normal-looking, fibrotic foci and hyperplastic areas by Laser-Capture-Microdissection. Gene expression analysis showed that 638 significantly different genes were identified that clearly distinguished the different IPF microenvironments . Among them, MMP19 was revealed as one of the most significantly up-regulated genes that distinguished normal looking epithelial cells (N) to hyperplastic epithelial cells, MMP19 up-regulation in IPF lungs was verified by immunohistochemical (IHC), qRT-PCR and Western-blot. IPF lungs are heterogeneity complex, which comprise normal looking area, fibrotic foci and hyperplastic area. In this study we separated the normal, fibrotic foci and hyperplastic area by LCM and employed Agilent whole genome gene expression microarray profiling to identify genes with the potential to distinguish the unique microenironment of IPF
2013-01-11 | E-GEOD-35309 | biostudies-arrayexpress
Project description:Contractile and highly synthetic myofibroblasts are the key effector cells involved in excessive extracellular matrix (ECM) deposition in multiple fibrotic conditions, including idiopathic pulmonary fibrosis (IPF). In order to define the key drivers of the fibrotic response, we used laser capture microdissection to isolate RNA from myofibroblasts within fibroblastic foci and performed microarray analysis in combination with a novel eigengene approach to identify functional clusters of genes which associate with collagen gene expression.
2020-10-28 | GSE98925 | GEO
Project description:MicroRNAs (miRs) are a class of non-coding RNAs of ~22nt long that play an important role in regulating gene expression at a post-transcriptional level. Aberrant levels of miRs have been associated with profibrotic processes in idiopathic pulmonary fibrosis (IPF). However, the majority of these studies used whole IPF tissue or in vitro monocultures in which fibrosis has been artificially induced. In this study, we used laser microdissection to collect fibroblastic foci (FF), the key pathological lesion in IPF, then isolate miRs and compare their expression levels to those found in whole IPF lung tissue and/or in vitro cultured fibroblast from IPF or normal lungs. Methods – LCM was utilised on formalin embedded IPF tissue to isolate multiple FF and isolate miRs. Libraries were generated and sequenced; data were bioinformatically analysed and Ingenuity Pathway Analysis (IPA) used for integration. Results - Our analysis revealed a total of 49 miRs differentially expressed in FF, of which only 7 were also differentially expressed in in vitro cultured fibroblast. This approach uncovered novel miRs that could be related to IPF. Conclusion - miR expression analyses in LCM isolated FF were able to identify up to 40 miRs not previously described in IPF. Differential expression of these miRs could potentially contribute to IPF development and progression.
2023-01-09 | GSE220107 | GEO
Project description:To further understand the pathologic microenvironment in IPF, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish normal and IPF lung in normal-looking, fibrotic foci and hyperplastic areas of IPF lung. Four IPF lungs were dissected into normal-looking, fibrotic foci and hyperplastic areas by Laser-Capture-Microdissection. Gene expression analysis showed that 638 significantly different genes were identified that clearly distinguished the different IPF microenvironments . Among them, MMP19 was revealed as one of the most significantly up-regulated genes that distinguished normal looking epithelial cells (N) to hyperplastic epithelial cells, MMP19 up-regulation in IPF lungs was verified by immunohistochemical (IHC), qRT-PCR and Western-blot.
2013-01-11 | GSE35309 | GEO
Project description:The Fibroblastic Focus (FF) is a lesion typical of Idiopathic Pulmonary Fibrosis (IPF). It is the site of myofibroblast accumulation and extracellular matrix (ECM) production. The molecular composition and function of the FF and surrounding tissue remain undefined. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogate the FF, adjacent mature scar tissue, and adjacent alveoli in 6 IPF specimens. To serve as a control, we perform LCM-MS on alveoli from 6 non-fibrotic controls.
2022-08-31 | PXD029341 | Pride
Project description:Cellular senescence is an irreversible cell growth arrest state linked to loss of tissue function and aging in mammals. The cellular transition from proliferation to senescence is marked by increased expression of the cell-cycle inhibitor p16INK4A and formation of senescence-associated heterochromatin foci (SAHF). It is known that SAHF formation depends primarily on HIRA-mediated nucleosome assembly of H3.3, and that the serine/threonine protein kinase Pak2 regulates HIRA-mediated nucleosome assembly of histone H3.3. Here, we tested the role of Pak2 in the regulation of cellular senescence. Depletion of Pak2 delays premature cellular senescence in both oncogene-induced senescence in human fibroblasts IMR90 cells and in oxidative stress induced senescence of mouse embryonic fibroblasts. Furthermore, overexpression of Pak2 promotes senescence of IMR90 cells. Importantly, depletion of Pak2 in mice delays the onset of some of the aging-associated phenotypes and extend life span of a progeroid mouse model. Lastly, we showed that Pak2 is required for expression of a group of genes involved in cellular senescence and regulates the deposition of newly synthesized H3.3 onto chromatin in senescent cells. Together, our results demonstrate that Pak2 is an important regulator of cellular senescence and organismal aging, in part through the regulation of gene expression and H3.3 nucleosome assembly.
2019-12-31 | GSE108081 | GEO
Project description:The gain-of-function MUC5B promoter varaint is the dominant risk for IPF development. Herein, we performed laser capture microdissection coupled mass spectrometry to isolate the characteristic histopathological lesions of IPF, the normal-appearing alveoli/small airways, and epithelium overlying fibroblastic foci. The captured samples were subject to mass spectrometry.
2025-06-13 | PXD058626 | Pride
Project description:Aberrant expression of master phenotype regulators by lung fibroblasts may play a central role in idiopathic pulmonary fibrosis (IPF). Interrogating IPF fibroblast transcriptome datasets, we identified Forkhead Box F1 (FOXF1), a DNA-binding protein required for lung development, as a candidate actor in IPF. Thus, we determined FOXF1 expression levels in fibroblasts cultured from normal or IPF lungs in vitro, and explored FOXF1 functions in these cells using transient and stable loss-of-function and gain-of-function models. FOXF1 mRNA and protein were expressed at higher levels in IPF compared with controls. In normal lung fibroblasts, FOXF1 repressed key fibroblast functions such as proliferation, survival, and expression of collagen-1 (COL1) and actin related protein 2/3 complex, subunit 2 (ARPC2). ARPC2 knockdown mimicked FOXF1 overexpression with regard to proliferation and COL1 expression. FOXF1 expression was induced by the antifibrotic mediator prostaglandin E2 (PGE2). Ex vivo, FOXF1 knockdown conferred CCL-210 lung fibroblasts the ability to implant and survive in uninjured mouse lungs. In IPF lung fibroblasts, FOXF1 regulated COL1 but not ARPC2 expression. In conclusion, FOXF1 functions and regulation were consistent with an antifibrotic role in lung fibroblasts. Higher FOXF1 levels in IPF fibroblasts may thus participate in a compensatory response to fibrogenesis. Lung fibroblasts derived from 4 different IPF patients (P313, P355, P375 and P426) were transiently transfected with pcfoxf1 or control pcDNA3.1-constructs. Total RNAs were extracted 24 h after transfection and hybridized on microarrays. One color experiment with 2 experimental conditions: pcfoxf1 and pcDNA3.1
2014-10-01 | E-GEOD-52612 | biostudies-arrayexpress
Project description:microRNA expression in fibroblastic foci within idiopathic pulmonary fibrosis lungs reveals novel disease relevant pathways.
| PRJNA908809 | ENA