PMID- 16164636 OWN - NLM STAT- MEDLINE DCOM- 20051230 LR - 20061115 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 68 IP - 4 DP - 2005 Oct TI - Matrix metalloproteinases and mesangial remodeling in light chain-related glomerular damage. PG - 1590-603 AB - 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. 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. FAU - Keeling, John AU - Keeling J AD - Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA. FAU - Herrera, Guillermo A AU - Herrera GA LA - eng PT - Journal Article PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Collagen Type IV) RN - 0 (Culture Media, Conditioned) RN - 0 (Immunoglobulin Light Chains) RN - 0 (RNA, Messenger) RN - 0 (Tenascin) RN - 0 (Tissue Inhibitor of Metalloproteinases) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - EC 3.4.24.23 (Matrix Metalloproteinase 7) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Amyloidosis/metabolism/*pathology/*physiopathology MH - Blotting, Western MH - Cells, Cultured MH - Collagen Type IV/metabolism MH - Culture Media, Conditioned MH - Enzyme-Linked Immunosorbent Assay MH - Glomerular Mesangium/*pathology/*physiology MH - Humans MH - Immunoglobulin Light Chains/metabolism MH - Immunohistochemistry MH - Matrix Metalloproteinase 1/genetics/metabolism MH - Matrix Metalloproteinase 2/genetics/metabolism MH - Matrix Metalloproteinase 3/genetics/metabolism MH - Matrix Metalloproteinase 7/genetics/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Matrix Metalloproteinases/*genetics/*metabolism MH - RNA, Messenger/analysis MH - Tenascin/metabolism MH - Tissue Inhibitor of Metalloproteinases/genetics EDAT- 2005/09/17 09:00 MHDA- 2005/12/31 09:00 CRDT- 2005/09/17 09:00 PHST- 2005/09/17 09:00 [pubmed] PHST- 2005/12/31 09:00 [medline] PHST- 2005/09/17 09:00 [entrez] AID - S0085-2538(15)51012-0 [pii] AID - 10.1111/j.1523-1755.2005.00571.x [doi] PST - ppublish SO - Kidney Int. 2005 Oct;68(4):1590-603. doi: 10.1111/j.1523-1755.2005.00571.x.