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Endothelial cell exosomes and fibroblast function

内皮细胞外泌体和成纤维细胞功能

基本信息

批准号：
10406146
负责人：
Anna Salapatas
金额：
$ 5.26万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10406146
关键词：
Affect Appearance Architecture Biological Assay Biological Process Blood Vessels Blood capillaries Caliber Cell Communication Cell Cycle Cell Proliferation Cells Cicatrix Collagen Communication Complex Custom Data Deposition Dermal Development Disease Elastin Endothelial Cells Exposure to Extracellular Matrix Extracellular Structure Fibroblasts Fibrosis Flow Cytometry Gene Expression Gene Targeting Generations Genomics Goals Growth Human Impairment In Vitro Infiltration Inflammatory Investigation Laboratories Lead Liver Lung Measures Mediating Medical Methods MicroRNAs Microscopy Myofibroblast Nutrient Outcome Oxygen Pathway Analysis Pathway interactions Phase Phenotype Physiological Polymerase Chain Reaction Process Protein Analysis Research Research Personnel Research Training Resources Sirius Red F3B Site Skin Small RNA Smooth Muscle Actin Staining Method Stains Time Tissues Training angiogenesis autocrine bioinformatics tool career development cell motility cell type craniofacial design differential expression exosome extracellular vesicles healing improved in vivo insight intradermal injection migration mouse model novel therapeutics paracrine psychologic repaired response second harmonic skeletal tissue repair tool transcriptome sequencing transcriptomics two-photon uptake wound wound bed wound healing

项目摘要

PROJECT SUMMARY/ABSTRACT This application proposes a customized research training plan designed to promote the development of the applicant into an independent investigator. The plan includes advanced training in laboratory experimentation, along with tailored professional and career development opportunities. The training plan is supported by the outstanding availability of local and institutional resources at UIC. The proposed research will examine cellular communication mechanisms that control scar formation, a common result of the healing response. In most tissues, the end result of tissue repair is a fibrous scar containing altered amounts and structure of the extracellular matrix components. Scarring and fibrosis occurs in numerous tissues and can create serious functional problems such as limited mobility, restricted skeletal growth, and weakened tissue strength that may lead to wound dehiscence. In the craniofacial region, scarring can impair both functionality as well as appearance, leading to a variety of physiologic and psychologic problems. Robust angiogenesis, a prominent feature of wound repair, includes the creation and then pruning of vessels. Angiogenesis is associated with increased fibrosis in numerous tissues including skin, lung, and liver. The goal of the proposed studies is to examine how the endothelial cells that arise during wound angiogenesis communicate with surrounding fibroblasts and how they influence their function and subsequent collagen deposition. One way that endothelial cells might communicate with fibroblasts is via small extracellular vesicles, called exosomes. The research plan utilizes traditional wound healing assays, methods for exosome purification and application, and small RNA and RNA sequencing tools to study exosome-mediated communication between these two cell types and to identify the resultant phenotypic changes in fibroblast activity. The central hypothesis of this research is that exosomes secreted from endothelial cells influence the phenotype of fibroblasts during wound healing and fibrosis. Our long-term goal is to understand how communication between endothelial cells and fibroblasts affects the scarring phenotype. Aim 1 will examine the effects of endothelial cell exosomes on fibroblast activity and fibrosis in vitro and in vivo. In vitro wound healing assays will be employed, and fibroblasts exposed to endothelial cell exosomes will be assessed for changes in migration, cell cycle phase, proliferation, and gene expression. An in vivo mouse model will be used to assess fibrosis and collagen architecture after intradermal injection on endothelial cell exosomes. Aim 2 will utilize bioinformatics tools to identify and characterize the specific miRNA cargo of endothelial cell exosomes that is mostly likely to impact fibroblast function at sites of scarring and fibrosis. Together, the Aims will lead to a better understanding of the mechanisms by which endothelial cells might modulate fibroblast function, and may lead to the development of novel therapeutics to treat fibrotic diseases.

项目总结/文摘