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Early prediction of inflammation by unprecedented unbiased linking of tissue molecular composition and structure

ABSTRACT: The identification of molecular signatures that aid early diagnosis of complex tissue pathologies, such as inflammatory diseases, poses a major scientific and clinical challenge due to their genetic and phenotypic heterogeneity. We have been able to unprecedentedly discover a distinct tissue state occurring before the onset of inflammatory clinical symptoms by integrating quantitative proteomics with advanced microscopy analyses. Through monitoring colonic extracellular matrix (ECM) remodeling in colitis animal models we have unexpectedly revealed that pre-symptomatic tissues display a unique ECM signature in terms of molecular composition, morphology and stiffness. By applying advanced computational analyses we were able to project quantitative proteomics data onto an axis correlating with spatially resolved tissue damage originating from the ECM. These results bridge the gap between tissue structure and composition while outlining the predictive power of the cellular microenvironment in early diagnostics of inflammatory diseases.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Colon

SUBMITTER: Tamar Geiger

LAB HEAD: Dr. Tamar Geiger

PROVIDER: PXD004740 | Pride | 2020-12-01

REPOSITORIES: Pride

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Source:

			Action	DRS
	Combined_IBD_proteomics.zip	Other
	Kermit_20150515_Ask_Ran_Elee_D10_1.raw	Raw
	Kermit_20150515_Ask_Ran_Elee_D10_10.raw	Raw
	Kermit_20150515_Ask_Ran_Elee_D10_2.raw	Raw
	Kermit_20150515_Ask_Ran_Elee_D10_3.raw	Raw

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Project description:The periodontium are the tissues supporting and investing the tooth and consists of the periodontal ligament, the gingiva, the root cementum, and the alveolar bone. The functions of the cell populations in health and disease regarding the host-mediated tissue destruction are not well understood. To get a first idea, of which genes might play a distinct role in chronic periodontal disease in vivo, we compared the genom-wide gene expressions of chronic inflamed and healthy periodontal ligament cells by microarray analysis and validated the data by real-time RT-PCR. The expression rates of 14.239 genes were investigated and 3.018 of them were found differentially expressed by at least two-fold, the expression rates of 1.451 genes were significantly up-regulated and the expression rates of 1.567 genes were significantly down-regulated in inflamed PDL cells. We focused on mainly structural components, for example, laminins and integrins, as well as degrading enzymes, for example, MMPs and cathepsins. The molecular composition of the laminin network varies in chronic inflamed compared to healthy PDL cells in vivo. Furthermore, integrin alpha6beta4, together with laminin-332, might be involved in chronic periodontal inflammation. Findings that diverse keratins were upregulated in chronic disease indicate that the epithelial cell rests of Malassez might also be involved in chronic periodontal inflammation. Also cathepsin B and cathepsin C might participate in the connective tissue destruction. The microarray analysis has identified a profile of genes potentially involved in chronic periodontal inflammation in vivo. Further studies are needed to entirely understand cellular activities during chronic periodontal inflammation in vivo. Experiment Overall Design: Periodontal tissue was collected from 32 patients at the Dental Medical School of the University of Goettingen (12 men, 20 women, aged between 18 and 72 years) from March 2005 to Dezember 2005. The tissue probes were taken from teeth, either extracted for orthodontic reasons (healthy periodontium) or because of chronic periodontal lesions. The differentiation between both collectives was performed using clinical and radiological parameters (clinical attachment loss, increase in probing depth, and radiographic bone loss). A detailed anamnesis of each patient was explored. All patients were without a medical history and were not on medication. In addition, the tissue samples used in our study were only taken from non-smokers. The extracted teeth were immediately frozen and stored at -80Â°C. All patients who participated in the study were informed about the nature and aim of this project and gave their written informed consent. The study was approved according to the regulations of the Ethics Committee of the Medical Faculty of the University of Goettingen.

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Early prediction of inflammation by unprecedented unbiased linking of tissue molecular composition and structure

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