Epithelial Transport in Disease: An Overview of Pathophysiology and Treatment

Clemente-Suárez, Vicente Javier; Martín-Rodríguez, Alexandra; Redondo-Flórez, Laura; Villanueva-Tobaldo, Carlota Valeria; Yáñez-Sepúlveda, Rodrigo; Tornero-Aguilera, José Francisco

doi:10.3390/cells12202455

Cited by 4 publications

(1 citation statement)

References 209 publications

(258 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like desmosomes, adherens junctions Transport via the transcellular pathways is the physiological route for nutrient absorption and it involves specific transporters, such as for amino acids, sugars, short-chain fatty acids (SCFAs) [5], or it can occur in a non-specific manner through endocytosis (transcytosis) [6]. Although transcellular transport is important in the context of disease, in particular relating to diarrhoea, it has little impact on gut leakiness [7]. On the other hand, paracellular transport is regulated by intercellular complexes, which could belong to one of three types: desmosomes, adherens and tight junctions (Figure 2A) [5].…”

Section: Key Elements In Barrier Permeabilitymentioning

confidence: 99%

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Schreiber,

Balas,

Robinson

et al. 2024

Cells

View full text Add to dashboard Cite

The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or “leaky gut”, has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes.

show abstract

Section: Key Elements In Barrier Permeabilitymentioning

confidence: 99%

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Schreiber,

Balas,

Robinson

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

Hong,

Tian,

Glynn

et al. 2024

Preprint

View full text Add to dashboard Cite

Fluid flow transport through the trabecular meshwork tissues is a major regulator of intraocular pressure (IOP) modulation in healthy and glaucomatous individuals. Microbead occlusion models of ocular hypertension regulate aqueous humor drainage to induce high IOP to allow for in vivo study of pressure-related glaucomatous pathology. However, the reliability and application of current injectable microbeads are hindered by inadequate design of the beads-tissue interfaces to maintain a stable IOP elevation over the long term. Considering the graded, porous architecture and fluid transport of the trabecular meshwork, we developed a tailored, injectable viscobeads technique, which induced a sustained elevation of IOP for at least 8 weeks. These composite viscobeads contain a non-degradable polystyrene (PS) core for structural support and a biodegradable polylactic-co-glycolic acid (PLGA) viscoelastic surface. This approach enhances the obstruction of aqueous humor drainage through heterogeneous sizes of trabecular meshwork fenestrations and reliably modulates the magnitude and duration of ocular hypertension. In a mouse model, a single viscobeads injection resulted in sustained IOP elevation (average 21.4+-1.39 mm Hg), leading to a 34% retinal ganglion cell (RGC) loss by 56 days. In an earlier stage of glaucoma progression, we conducted non-invasive electroretinography (ERG) recording and revealed glaucomatous progression by analyzing high-frequency oscillatory potentials. To further explore the application of the viscobeads glaucoma models, we assayed a series of genes through adeno-associated virus (AAV)-mediated screening in mice and assessed the impact of genetic manipulation on RGC survivals. CRISPR mediated disruption of the genes, PTEN, ATF3 and CHOP enhanced RGC survival while LIN 28 disruption negatively impacted RGC survival. This biologically driven viscobeads design provides an accessible approach to investigate chronic intraocular hypertension and glaucoma-like neurodegeneration and ultimately tenders the opportunity to evaluate genetic and pharmacological therapeutics.

show abstract

A subset of human choroid plexus epithelial cells exhibit mitochondrial eccentricity and distinct expression of the pigmentation-associated enzyme TYRP1

Groh,

Premachandran,

Creeggan

et al. 2024

Preprint

View full text Add to dashboard Cite

For decades, ultrastructural evaluation of epithelial cells in diverse organ systems has demonstrated the existence of two subtypes identified by stark differences in cytoplasmic electron density — so-called light and dark epithelial cells. Choroid plexus (CP) epithelial cells are key regulators of CSF homeostasis and are one of many specialized epithelial linings that exhibit this bimodal phenotype. Despite longstanding acknowledgement, it has been difficult to assess the potential significance of adult human light and dark CP epithelial cells due to a lack of characterization beyond electron microscopy (EM). We present the first transcriptomic analysis of adult human CP epithelial cells and denote the existence of four epithelial subpopulations, one of which is defined by elevated expression ofTYRP1— a melanocyte-associated tyrosine-related protein involved in cellular pigmentation and proliferation.TYRP1-high cells also downregulate genes related to cilia function (which is consistent with observations of dark cell identity in organoids) and upregulate genes associated with pathways related to cell cycling, stress, and iron regulation. Our data provide an explanation of the molecular underpinning of adult human light and dark cell identity and serve as a resource for investigations of epithelial heterogeneity in the CP and other organs where dark cells are found.

show abstract

Epithelial Transport in Disease: An Overview of Pathophysiology and Treatment

Cited by 4 publications

References 209 publications

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Border Control: The Role of the Microbiome in Regulating Epithelial Barrier Function

Biologically Driven In Vivo Occlusion Design Provides a Reliable Experimental Glaucoma Model

A subset of human choroid plexus epithelial cells exhibit mitochondrial eccentricity and distinct expression of the pigmentation-associated enzyme TYRP1

Contact Info

Product

Resources

About