What is epithelial dysfunction?

Epithelial dysfunction refers to abnormalities or impaired function of epithelial cells, which are specialized cells that line the surfaces of organs and structures throughout the body. Epithelial cells form protective barriers that separate different compartments within the body and regulate the exchange of molecules, ions, and fluids between these compartments. Epithelial dysfunction can occur in various organs and tissues, leading to disruptions in normal physiological processes and contributing to the pathogenesis of various diseases.


Epithelial dysfunction can manifest in different ways depending on the specific tissue or organ involved. Some common examples include:


  • Respiratory Epithelial Dysfunction: Dysfunction of the respiratory epithelium can lead to conditions such as asthma, chronic obstructive pulmonary disease (COPD), and respiratory infections. In asthma, for example, epithelial dysfunction is characterized by increased permeability of the airway epithelium, altered mucin production, and impaired barrier function, contributing to airway inflammation and hyperresponsiveness.


  • Intestinal Epithelial Dysfunction: Dysfunction of the intestinal epithelium can lead to gastrointestinal disorders such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and intestinal infections. In IBD, epithelial dysfunction is characterized by increased intestinal permeability, impaired mucosal barrier function, and dysregulated immune responses, leading to chronic inflammation and tissue damage.


  • Renal Epithelial Dysfunction: Dysfunction of the renal epithelium can lead to kidney disorders such as acute kidney injury (AKI), chronic kidney disease (CKD), and renal tubular disorders. In AKI, for example, epithelial dysfunction may result from ischemic injury, nephrotoxic insults, or inflammatory processes, leading to disruption of tubular epithelial cell function and impaired renal function.


  • Epithelial Dysfunction in Skin: Dysfunction of the epidermal epithelium can lead to skin disorders such as eczema, psoriasis, and impaired wound healing. In eczema, for example, dysfunction of the skin barrier (stratum corneum) can lead to increased permeability, dryness, and inflammation, predisposing individuals to allergic reactions and skin infections.


  • Epithelial Dysfunction in Blood Vessels: Dysfunction of the endothelial cells lining blood vessels can lead to vascular disorders such as atherosclerosis, hypertension, and thrombosis. Endothelial dysfunction is characterized by impaired production of vasodilators (such as nitric oxide) and increased expression of adhesion molecules, leading to inflammation, vasoconstriction, and thrombosis.


What is the relationship between epithelial dysfunction and oxidative stress?

The relationship between epithelial dysfunction and oxidative stress is bidirectional, with oxidative stress playing a significant role in the development and progression of epithelial dysfunction, while epithelial dysfunction can also contribute to oxidative stress through various mechanisms. Here’s how these two processes interact:


  • Oxidative Stress-Induced Epithelial Dysfunction:
    • Oxidative stress can directly damage epithelial cells by causing oxidative modifications to lipids, proteins, and DNA, leading to impaired cellular function and integrity.
    • ROS can disrupt the structure and function of epithelial junctions, such as tight junctions and adherens junctions, which are crucial for maintaining epithelial barrier integrity. Disruption of these junctions can increase epithelial permeability and impair barrier function.
    • ROS can activate signaling pathways involved in inflammation, apoptosis, and fibrosis within epithelial cells, leading to tissue injury and dysfunction. For example, ROS-mediated activation of nuclear factor kappa B (NF-κB) signaling can promote the expression of pro-inflammatory cytokines and adhesion molecules, exacerbating inflammation and tissue damage.


  • Epithelial Dysfunction-Induced Oxidative Stress:
    • Epithelial dysfunction can lead to the release of pro-inflammatory cytokines, chemokines, and damage-associated molecular patterns (DAMPs), which can activate immune cells and stimulate ROS production. For example, in inflammatory bowel disease (IBD), dysfunctional intestinal epithelium can release inflammatory mediators that promote oxidative stress in the gut mucosa.
    • Impaired barrier function in epithelial tissues can lead to increased exposure of underlying cells to environmental toxins, pathogens, and inflammatory stimuli, which can stimulate ROS production and exacerbate oxidative stress.
    • Epithelial dysfunction can disrupt antioxidant defenses within epithelial cells, leading to decreased scavenging of ROS and increased susceptibility to oxidative damage. For example, dysfunction of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase can impair the ability of epithelial cells to neutralize ROS.


Overall, oxidative stress and epithelial dysfunction are closely intertwined processes that can perpetuate each other and contribute to the pathogenesis of various diseases and conditions.