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

Abstract

Background. 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. Methods. 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 microdis-section and selective MMP microarray. Zymography was used to assess MMP activity. Results. 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. Conclusion. 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. © 2005 by the International Society of Nephrology.