Files and links (1)
Published, Version of Record (VoR)Open Access (License Unspecified), Open
Journal article
Ras Mutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes
Molecular biology of the cell, v 16(12), pp 5538-5550
Dec 2005
PMID: 16176977
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although ras mutations have been shown to affect epithelial architecture and polarity, their role in altering tight junctions remains unclear. Transfection of a valine-12 mutated ras construct into LLC-PK
1
renal epithelia produces leakiness of tight junctions to certain types of solutes. Transepithelial permeability of d-mannitol increases sixfold but transepithelial electrical resistance increases >40%. This indicates decreased paracellular permeability to NaCl but increased permeability to nonelectrolytes. Permeability increases to d-mannitol (M
r
182), polyethylene glycol (M
r
4000), and 10,000-M
r
methylated dextran but not to 2,000,000-M
r
methylated dextran. This implies a “ceiling” on the size of solutes that can cross a ras-mutated epithelial barrier and therefore that the increased permeability is not due to loss of cells or junctions. Although the abundance of claudin-2 declined to undetectable levels in the ras-overexpressing cells compared with vector controls, levels of occludin and claudins 1, 4, and 7 increased. The abundance of claudins-3 and -5 remained unchanged. An increase in extracellular signal-regulated kinase-2 phosphorylation suggests that the downstream effects on the tight junction may be due to changes in the mitogen-activated protein kinase signaling pathway. These selective changes in permeability may influence tumorigenesis by the types of solutes now able to cross the epithelial barrier.
Metrics
Details
- Title
- Ras Mutation Impairs Epithelial Barrier Function to a Wide Range of Nonelectrolytes
- Creators
- James M. Mullin - Lankenau Institute for Medical ResearchJames M. Leatherman - Lankenau Institute for Medical ResearchMary Carmen Valenzano - Lankenau Institute for Medical ResearchErika Rendon Huerta - Lankenau Institute for Medical ResearchJon Verrechio - Division of Gastroenterology, Lankenau Hospital, Wynnewood, PA 19096David M. Smith - Division of Gastroenterology, Lankenau Hospital, Wynnewood, PA 19096Karen Snetselaar - Saint Joseph's UniversityMantao Liu - Lankenau Institute for Medical ResearchMary Kay Francis - Villanova UniversityChristian Sell - Lankenau Institute for Medical Research
- Publication Details
- Molecular biology of the cell, v 16(12), pp 5538-5550
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000233626000007
- Scopus ID
- 2-s2.0-28644445404
- Other Identifier
- 991020100073104721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology