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Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Morphological changes and pathology of mouse glomeruli infected with a streptococcal L-form or exposed to
Abstract:
The morphology and pathology of cultured mouse glomeruli were examined at the cellular and subcellular levels after infection with a physiological isotonic L-form of Streptococcus pyogenes type 12 or exposure to streptococcal lipoteichoic acid. These changes, as viewed by light microscopy, were identical regardless of the method used to induce glomerular cytotoxicity. They were characterized by an initial reduction in the outgrowth of cells, some cellular granulation, and later, destruction of the confluent monolayer. Once initiated, cytotoxicity could not be reversed by refeedings, and complete glomerular destruction resulted after 2 weeks. Electron microscope studies revealed that the basement membrane of intact glomeruli exposed to streptococcal lipoteichoic acid had become greatly thickened (two- to fourfold) and electron dense. Our recent biochemical findings have shown that streptococcal lipoteichoic acid increases the amount of collagen formed and retained by mouse fibroblasts in tissue culture as well as causing a reduction in the hydroxylation of proline in both intracellular and secreted collagenous material (Leon and Panos, Infect. Immun. 40:785-794, 1983). These results, together with the present findings, suggest that the thickening of the glomerular basement membrane may be due to defective collagen biosynthesis as a result of streptococcal lipoteichoic acid. The use of cultured glomeruli as a model system for studying the earliest basement membrane alterations in the absence of an immune response as a result of streptococcal lipoteichoic acid is suggested.
Insights
Streptococcus pyogenes lipoteichoic acid causes mouse glomerular damage by thickening the basement membrane. This suggests defective collagen biosynthesis may underlie the observed kidney pathology.
Area of Science:
- Nephrology
- Microbiology
- Biochemistry
Background:
- Streptococcus pyogenes infection can lead to kidney damage.
- Lipoteichoic acid is a component of Streptococcus pyogenes.
Purpose of the Study:
- To investigate the effects of Streptococcus pyogenes and its lipoteichoic acid on cultured mouse glomeruli.
- To elucidate the cellular and subcellular mechanisms of glomerular injury.
Main Methods:
- Cultured mouse glomeruli were exposed to Streptococcus pyogenes L-form or streptococcal lipoteichoic acid.
- Light and electron microscopy were used to assess glomerular morphology and pathology.
- Biochemical analysis examined collagen synthesis and proline hydroxylation.
Main Results:
- Both Streptococcus pyogenes and lipoteichoic acid induced identical glomerular cytotoxicity, including cell granulation and monolayer destruction.
- Electron microscopy revealed significant thickening and increased electron density of the glomerular basement membrane.
- Biochemical assays showed lipoteichoic acid increased collagen production and decreased proline hydroxylation in fibroblasts.
Conclusions:
- Streptococcal lipoteichoic acid induces glomerular basement membrane thickening, likely due to defective collagen biosynthesis.
- Cultured glomeruli provide a model to study early basement membrane alterations without immune responses.
- This research suggests a mechanism for kidney pathology following Streptococcus pyogenes infections.
