자료유형  

 학위논문

Control Number  

0017162482

International Standard Book Number  

9798384465362

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Resnikoff, Henry Alexander .

Publication, Distribution, etc. (Imprint  

[S.l.] : Princeton University., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

117 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

General Note  

Advisor: Schwarzbauer, Jean E.

Dissertation Note  

Thesis (Ph.D.)--Princeton University, 2024.

Summary, Etc.  

요약The extracellular matrix (ECM) is a 3-dimensional network of proteins, proteoglycans, and glycoproteins organized into complex structures that support tissue specific cell attachment, arrangement, and behavior. Fibronectin (FN) is a foundational ECM protein that is polymerized into fibrils by cells and helps coordinate cell adhesion, migration, and proliferation. FN is essential for cardiovascular development and supports angiogenesis in adults. Despite its noted role in vasculogenesis, the basement membrane, a highly organized ECM that underlies endothelial cells in established vasculature, notably lacks FN. However, in fibrosis, FN accumulates in the subendothelial space, disrupting the normal basement membrane architecture. Utilizing human umbilical vein endothelial cells (HUVECs) cultured on permeable Transwell membranes, we investigated how FN matrix accumulation impacts endothelial cell organization and function. We found the FN matrix assembled in this model is heterogenous and discontinuous, and sites of FN matrix accumulation, driven by exogenous FN supplementation, correlated with regional alterations to cell distribution and cell cycle entry. Time course analysis revealed that FN accumulation preceded other changes, demonstrating a causal link between FN accumulation and monolayer disruption. Functionally, FN accumulation increased the HUVEC monolayer permeability to large solutes and induced increased MDA-MB-231 cell attachment to the monolayer, due to the exposure of subendothelial matrix. These results demonstrate that FN mediates a disruption of endothelial cell barrier function, supporting the hypothesis that FN is causative of pathological vascular dysfunction in fibrosis. We subsequently demonstrate the utility of a FN targeting probe generated from a novel, phage-display derived peptide, for delivering and maintaining fluorescent signal to the FN matrix, thus expanding the toolbox for analyzing and targeting FN matrix.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Immunology.

Index Term-Uncontrolled  

Extracellular matrix

Index Term-Uncontrolled  

Fibronectin

Index Term-Uncontrolled  

Endothelial cells

Index Term-Uncontrolled  

Cell adhesion

Index Term-Uncontrolled  

Cell attachment

Added Entry-Corporate Name  

Princeton University Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 86-04B.

Electronic Location and Access  

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Control Number  

joongbu:657173