DSS-induced damage to basement membranes is repaired by matrix replacement and crosslinking
Year: 2019
Type: article
Abstract: ABSTRACT Basement membranes are an ancient form of animal extracellular matrix. As important structural and functional components of tissues, basement membranes are subject to environmental damage and must be repaired while maintaining functions. Little is known about how basement membranes get repaired. This paucity stems from a lack of suitable in vivo models for analyzing such repair. Here, we show that dextran sodium sulfate (DSS) directly damages the gut basement membrane when fed to adult Drosophila. DSS becomes incorporated into the basement membrane, promoting its expansion while decreasing its stiffness, which causes morphological changes to the underlying muscles. Remarkably, two days after withdrawal of DSS, the basement membrane is repaired by all measures of analysis. We used this new damage model to determine that repair requires collagen crosslinking and replacement of damaged components. Genetic and biochemical evidence indicates that crosslinking is required to stabilize the newly incorporated repaired Collagen IV rather than to stabilize the damaged Collagen IV. These results suggest that basement membranes are surprisingly dynamic.
Source: Journal of Cell Science
DOI: 10.1242/jcs.226860
Institutions: Vanderbilt University, Vanderbilt University Medical Center
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Funders: Burroughs Wellcome Fund, National Institutes of Health, National Heart, Lung, and Blood Institute, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Extramural Research, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1331061530, G1344704808, Investigating the mechanisms of beta cardiac myosin II during sarcomere formation and function, G1806196891, G1971342940, G2019238319, G2704391173, G2914309916, Vanderbilt Mouse Metabolic Phenotyping Center, G407372463, Vanderbilt Mouse Metabolic Phenotyping Center, G4157836929, Initiative for Maximizing Student Development, Training Program in Stem Cell and Regenerative Developmental Biology, G725763919, G7357063788, G892006870, Molecular and Cellular Basis for Digestive Diseases, Vanderbilt Diabetes Research Center, The assembly and function of cellular contractile systems, Core Grant in Vision Research
OpenAlex ID: W2918328100