Cell Biology – Immunology – Pathology

Kidney International (2005) 68, 1590–1603; doi:10.1111/j.1523-1755.2005.00571.x

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

JOHN KEELING and GUILLERMO A HERRERA

Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and Department of Medicine, Louisiana State University Health Sciences Center, Shreveport, Louisiana

Correspondence: Guillermo A. Herrera, M.D., Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, 1501 Kings Highway, Shreveport, LA 71130. E-mail: gherre@lsuhsc.edu

Received 10 March 2005; Revised 23 April 2005; Accepted 9 May 2005.

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Abstract

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.

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.

Keywords:

AL-amyloidosis (AL-Am), kidney, light chain deposition disease (LCDD), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs)

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