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


CONCLUSIONS
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.
Keeling
John
J
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
Herrera
Guillermo A
GA
D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D015153:Blotting, Western; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D005920:Glomerular Mesangium / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism; D007150:Immunohistochemistry; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019063:Tenascin / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics
D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D007147:Immunoglobulin Light Chains; D012333:RNA, Messenger; D019063:Tenascin; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1