Complexities of the glomerular basement membrane
TL;DR: How studies of GBM composition and structure have provided insights into GBM assembly, its developmental transitions and its role in glomerular filtration are described, and current and potential future treatments for these disorders are discussed.
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Abstract: The glomerular basement membrane (GBM) is a key component of the glomerular capillary wall and is essential for kidney filtration. The major components of the GBM include laminins, type IV collagen, nidogens and heparan sulfate proteoglycans. In addition, the GBM harbours a number of other structural and regulatory components and provides a reservoir for growth factors. New technologies have improved our ability to study the composition and assembly of basement membranes. We now know that the GBM is a complex macromolecular structure that undergoes key transitions during glomerular development. Defects in GBM components are associated with a range of hereditary human diseases such as Alport syndrome, which is caused by defects in the genes COL4A3, COL4A4 and COL4A5, and Pierson syndrome, which is caused by variants in LAMB2. In addition, the GBM is affected by acquired autoimmune disorders and metabolic diseases such as diabetes mellitus. Current treatments for diseases associated with GBM involvement aim to reduce intraglomerular pressure and to treat the underlying cause where possible. As our understanding about the maintenance and turnover of the GBM improves, therapies to replace GBM components or to stimulate GBM repair could translate into new therapies for patients with GBM-associated disease. The glomerular basement membrane (GBM) is essential for kidney filtration. This Review describes how studies of GBM composition and structure have provided insights into GBM assembly, its developmental transitions and its role in glomerular filtration. The authors also discuss GBM-associated diseases and current and potential future treatments for these disorders.
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TL;DR: The need for future work to further delineate the immunopathogenic mechanisms of anti-GBM disease, and how to better refine and improve treatments, is highlighted, particularly for patients presenting with adverse prognostic factors.
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Jeffrey H. Miner,Joshua R. Sanes +1 more
TL;DR: Interestingly, numerous changes in the molecular composition of glomerular BL precede the onset of renal dysfunction; these include loss of collagens alpha 4 and alpha 5(IV), retention of collagen alpha 1/2(IV, appearance of fibronectin and collagen VI, and increased levels of perlecan.
Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture
A. Scott McCall,Christopher F. Cummings,Gautam Bhave,Roberto M. Vanacore,Roberto M. Vanacore,Andrea Page-McCaw,Andrea Page-McCaw,Billy G. Hudson +7 more
TL;DR: It is established that Br(-) is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development, and its deficiency may be relevant to BM alterations observed in nutritional and smoking-related disease.
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