Studies of tissue barriers: Regulation of phenotype and transport across the epithelium and endothelium

BCH 2024H

Maintenance and regulation of barrier function – which protects the body from a potentially hostile external environment – and separates the vascular system from the tissues it supplies – is a recurring theme in medicine. Defects in barrier function lie at the heart of numerous diseases, including acute respiratory distress syndrome, atherosclerosis and chronic kidney disease.

This course will discuss the mechanisms of barrier function, which is constituted by specialized cells known as the endothelium in blood vessels and, at the interface with the external environment, are made up of the epithelium. Their proper regulation is critical for tissue integrity and normal physiology. For instance, since every blood vessel in the body is lined by endothelial cells, one of the fundamental functions of the endothelial layer is to regulate the passage of cells, fluids and molecules in and out of the vasculature. Large molecules (e.g. >10 nm) can only traverse healthy continuous endothelium by endothelial transcytosis; for instance, this is the mechanism by which low density lipoprotein (LDL) cholesterol accumulates in the subendothelial intima in the early stages of atherosclerosis. In contrast, under inflammatory conditions, intercellular gaps develop leading to paracellular endothelial leakage. How this can be attenuated without compromising the innate immune response is an area of active research.

Similarly, the epithelium is the vital boundary that separates the external environment from the internal milieu of the body. Accordingly, epithelial integrity is essential for practically all physiological functions, and, conversely, epithelial injury is a key initiator and pathogenic factor in a large variety of diseases. Disruption of the epithelium perturbs vectorial transport processes that underlie all fluid and solute secretion and resorption in the body, while harm to the epithelium may initiate reactive or adaptive epithelial responses often leading to dysregulated tissue repair that manifests in chronic organ scarring, known as fibrosis. Integrity of intercellular contacts also regulates gene transcription and thereby phenotype, partly via the cytoskeleton, which in turn affects the nucleocytoplasmic traffic of transcription factors. Understanding mechanisms is of key importance since fibrosis ultimately destroys the architecture of parenchymal organs, such as lung, liver and kidney, and is thought to contribute to 45% of all deaths in the western world.

Course Next Offered

Winter 2019

Course Time and Location

Thursday's, 10:00 - 11:30 am, MSB Room 5231 (*note exception Jan. 31)

Jan 10, 17, 24: 10:00 - 11:00 am, MSB Room 5231
Jan 31: 11:00 am: 12:30 pm, MSB Room 7231
Feb 7, 14, 21, 28: 10:00 - 11:00 am, MSB Room 5231


Enrollment Limit

Yes — 10

Method of Student Evaluation

1) Attendance and participation 20%
2) Grant proposal 40%
3) Journal article presentation 40%

Coordinator

Warren L. Lee

Warren L. Lee

St. Michael's Hospital
LKS, Room 613
416-864-6060-77656
warren.lee@unityhealth.to

Andras Kapus

Andras Kapus

Keenan Centre for Biomedical Research
209 Victoria Street, Room 621
416-847-1751
KapusA@smh.ca

Last Updated 12 September 2018