Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage

• Published in: Kidney international Vol. 68; no. 4; pp. 1590 - 1603
• Main Authors: Keeling, John, Herrera, Guillermo A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2005; Nature Publishing; Elsevier Limited
• Subjects: AL-amyloidosis (AL-Am); Amyloidosis - metabolism; Amyloidosis - pathology; Amyloidosis - physiopathology; Biological and medical sciences; Blotting, Western; Cells, Cultured; Collagen Type IV - metabolism; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Glomerular Mesangium - pathology; Glomerular Mesangium - physiology; Humans; Immunoglobulin Light Chains - metabolism; Immunohistochemistry; kidney; light chain deposition disease (LCDD); Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 7 - metabolism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; matrix metalloproteinases (MMPs); Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Medical sciences; Nephrology. Urinary tract diseases; RNA, Messenger - analysis; Tenascin - metabolism; Tissue Inhibitor of Metalloproteinases - genetics; tissue inhibitors of metalloproteinases (TIMPs); matrix metalloproteinases (MMPs); light chain deposition disease (LCDD); kidney; tissue inhibitors of metalloproteinases (TIMPs); AL-amyloidosis (AL-Am); AL amyloidosis; Nephrology; Disease; Enzyme; Metalloendopeptidases; Light peptide chain; Remodeling; Tissue inhibitor metalloproteinase; Kidney; Urology; Renal glomerulus; Peptidases; Urinary system; Hydrolases; Lesion; Deposition
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1111/j.1523-1755.2005.00571.x

Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. Matrix metalloproteinases (MMPs) belong to the zinc endopeptidase subgroup of the metalloproteinase superfamily and are primarily involved in extracellular matrix (ECM) remodeling. Alterations of the mesangial ECM in AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD) are crucial in their pathogeneses as two divergent entities. Protein expression patterns of five MMPs (MMP-1, 2, 3, 7, and 9) in renal tissues obtained from autopsies and kidney biopsies, and cultured human mesangial cells (HMCs) treated with light chains obtained from the urines of patients with AL-Am and LCDD were analyzed. MMP mRNA expressions were determined in glomeruli following laser capture microdissection and selective MMP microarray. Zymography was used to assess MMP activity. The average glomerular MMP expression was 6 times greater in AL-Am than LCDD and negative control renal tissues with different expression profiles: MMP-1, 7 > 9 > 3 > 2, MMP-1 > 2, 9 > 3 > 7, and MMP-2, 3, 7 > 9 > 1, respectively. Microdissected glomeruli and HMCs treated with light chains expressed higher levels of MMP mRNA and proteins in AL-Am than LCDD. Zymography was used to assess activity demonstrating increased MMP-2 in AL-Am. Altered expressions of MMPs play a key role in the pathogenesis of AL-Am and LCDD. MMPs were more highly expressed in AL-Am compared to LCDD.