ArticleThe American journal of pathology2006
Role for macrophage metalloelastase in glomerular basement membrane damage associated with alport syndrome.
Article in The American journal of pathology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 85 citations in OpenAlex.
- Genotype-Based Molecular Mechanisms in Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2025Review
- Collagen formation, function and role in kidney disease.Nature reviews. Nephrology · 2025Review
- Sensory nerve-secreted factors regulate basal keratinocyte functionIntegrative organismal biology (Oxford, England) · 2025Article
- Matrix metalloproteinases in kidney homeostasis and diseases: an update.American journal of physiology. Renal physiology · 2024Review
- Propagermanium as a Novel Therapeutic Approach for the Treatment of Endothelial Dysfunction in Type 2 Diabetes.International journal of molecular sciences · 2024Article
- Ramipril therapy in integrin α1-null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA-seq analysis.The Journal of pathology · 2024Article
- Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1.The Journal of pathology · 2022Article
- Tensin 2-deficient nephropathy: mechanosensitive nephropathy, genetic susceptibility.Experimental animals · 2022Review
- Molecular and Cellular Mechanisms Underlying the Initiation and Progression of Alport Glomerular Pathology.Frontiers in medicine · 2022Review
- Molecular Basis, Diagnostic Challenges and Therapeutic Approaches of Alport Syndrome: A Primer for Clinicians.International journal of molecular sciences · 2021Review
- A glycine substitution in the collagenous domain of Col4a3 in mice recapitulates late onset Alport syndrome.Matrix biology plus · 2021Article
- A type IV collagenase inhibitor, N-hydroxy-3-phenyl-2-(4-phenylbenzenesulfonamido) propanamide (BiPS), suppresses skin injury induced by sulfur mustard.Toxicology and applied pharmacology · 2020Article
- Glomerular endothelial cell heterogeneity in Alport syndrome.Scientific reports · 2020Article
- Propagermanium administration for patients with type 2 diabetes and nephropathy: A randomized pilot trial.Endocrinology, diabetes & metabolism · 2020Article
- Modification of an aggressive model of Alport Syndrome reveals early differences in disease pathogenesis due to genetic background.Scientific reports · 2019Article
- Potentials of C-C motif chemokine 2-C-C chemokine receptor type 2 blockers including propagermanium as anticancer agents.Cancer science · 2019Review
- Lysyl oxidase like-2 contributes to renal fibrosis in Col4α3/Alport mice.Kidney international · 2018Article
- Basement Membrane Defects in Genetic Kidney Diseases.Frontiers in pediatrics · 2018Review
- Characterization of the early molecular changes in the glomeruli of Cd151Scientific reports · 2017Article
- Podocyte-specific chemokine (C-C motif) receptor 2 overexpression mediates diabetic renal injury in mice.Kidney international · 2017Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Alport syndrome is a glomerular basement membrane (GBM) disease caused by mutations in type IV collagen genes. A unique irregular thickening and thinning of the GBM characterizes the progressive glomerular pathology. The metabolic imbalances responsible for these GBM irregularities are not known. Here we show that macrophage metalloelastase (MMP-12) expression is >40-fold induced in glomeruli from Alport mice and is markedly induced in glomeruli of both humans and dogs with Alport syndrome. Treatment of Alport mice with MMI270 (CGS27023A), a broad spectrum MMP inhibitor that blocks MMP-12 activity, results in largely restored GBM ultrastructure and function. Treatment with BAY-129566, a broad spectrum MMP inhibitor that does not inhibit MMP-12, had no effect. We show that inhibition of CC chemokine receptor 2 (CCR2) receptor signaling with propagermanium blocks induction of MMP-12 mRNA and prevents GBM damage. CCR2 receptor is expressed in glomerular podocytes of Alport mice, suggesting MCP-1 activation of CCR2 on podocytes may underlie induction of MMP-12. These data indicate that the irregular GBM that characterizes Alport syndrome may be mediated, in part, by focal degradation of the GBM due to MMP dysregulation, in particular, MMP-12. Thus, MMP-12/CCR2 inhibitors may provide a novel and effective therapeutic stra-tegy for Alport glomerular disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.