Unknown,Transcriptomics,Genomics,Proteomics

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Feedback amplication of fibrosis through matrix stiffening and COX-2 suppression

ABSTRACT: We tested the hypothesis that increasing matrix stiffness on which normal human lung fibroblasts are grown promotes the expression of a fibrogenic cellular transcriptomic program. Keywords: Human lung fibroblast, matrix stiffness, PTGS2, COX-2, Prostaglandin E2 Total RNA extracted from normal human lung fibroblasts from 3 human subjects and separately grown on 5 discrete matrix stiffness conditions: 100, 400, 1600, 6400, 25600 Pascals.

ORGANISM(S): Homo sapiens

SUBMITTER: Alvin Kho

PROVIDER: E-GEOD-22011 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression.

Liu Fei F Mih Justin D JD Shea Barry S BS Kho Alvin T AT Sharif Asma S AS Tager Andrew M AM Tschumperlin Daniel J DJ

The Journal of cell biology 20100801 4

Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and mat ...[more]

PMID: 20733059

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Project description:Rationale: Maternal immune responses can promote allergy development in offspring. Pilot data show that neonates of mother mice exposed during pregnancy to air pollution particles have increased allergic susceptibility. Objective: We investigated whether inflammatory response to titanium dioxide (TiO2) particles earlier considered immunologically âinertâ is enhanced during pregnancy. Methods: Pregnant BALB/c mice (or non-pregnant controls) received particle suspensions intranasally at day 14 of pregnancy. Lung inflammatory responses were evaluated 19 and 48 h after exposure. Results: Pregnant mice showed robust and persistent acute inflammatory responses after exposure to TiO2, while non-pregnant females had the expected minimal responses. Genomic profiling identified genes differentially expressed in pregnant lungs exposed to TiO2. Neonates of mothers exposed to TiO2 (but not PBS) developed increased susceptibility to allergens. Conclusion: Pregnancy enhances lung inflammatory responses to otherwise relatively innocuous inert particles. Experiment Overall Design: To test whether pregnancy alters the normally minimal inflammatory response to âinertâ particles, we have administered TiO2 and DEP suspensions (50 ug/mouse) or PBS solution by intranasal insufflation to normal or pregnant E14 mice (see Figure 1B). The mice were subjected to pathologic analysis 19 or 48 hrs later. Experiment Overall Design: Respirable-size TiO2 particles were generously provided by Dr. Ian Gilmour (US EPA). Particle samples were baked at 165 0C for 3 h to eliminate endotoxin, aliquoted and stored frozen at â 80 0C. Particle suspensions (50 ug in 50 uL) or PBS solution (vehicle) were administered by single intranasal insufflation of pregnant or normal Balb/c mice under light halothane anesthesia Experiment Overall Design: Total lung RNA extraction and isolation was performed 19 hrs after exposure using a Qiagen RNAeasy Mini kit according to manufacturerâs instructions (Qiagen, Valencia, CA). RNA purity and quality were analyzed by Agilent Bioanalyzer 2100 scan. The hybridization was carried out at the Harvard Partners Genomic Center Microarray facility (Cambridge, MA) using the Affymetrix GeneChip Â® platform and Affymetrix mouse 430 2.0 chips (Affymetrix, Santa Clara, CA). Experiment Overall Design: 4 samples were analyzed in each of 4 groups: Normal PBS, Normal TiO2, Pregnant PBS and Pregnant TiO2, for a total of 16 samples.

Dataset Information

Feedback amplication of fibrosis through matrix stiffening and COX-2 suppression

Publications

Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression.

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