Abstract | BACKGROUND: In interstitial fibrosis, monocytes and myofibroblasts have been directly implicated in scarring, apoptosis, and tissue necrosis. While much has been done to explore the role of these cell types individually in fibrosis, the interactive dependency of monocytes and myofibroblasts has been only marginally explored. METHODS: RESULTS: Treated mice showed a markedly reduced accumulation of matrix proteins. Tissue monocytes express TGF-beta 1 mRNA, and TGF-beta 1 is required for myofibroblast accumulation. The number of apoptotic cells was not influenced by TGF-beta 1 inhibition. Monocytes express MMP-2, MMP-9, TIMP-2, and TIMP-3. MMP activity and mRNA expression is equally up regulated in treated and untreated Alport mice. Tubular basement membranes (TBM) around clusters of monocytes are notably degraded. TGF-beta 1 inhibition does not extend the life of Alport mice. CONCLUSION: These studies demonstrate that monocytes may influence myofibroblast accumulation via TGF-beta1, and that monocytes, and not myofibroblasts, are associated with tubular atrophy in Alport mice. Elevated MMP expression and activity is associated with TBM destruction near monocytes clusters, suggesting an anoikis mechanism may contribute to apoptosis in this model.
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Authors | Kathyrn D Rodgers, Velidi Rao, Daniel T Meehan, Nicole Fager, Philip Gotwals, Sarah T Ryan, Victor Koteliansky, Ryoichi Nemori, Dominic Cosgrove |
Journal | Kidney international
(Kidney Int)
Vol. 63
Issue 4
Pg. 1338-55
(Apr 2003)
ISSN: 0085-2538 [Print] United States |
PMID | 12631350
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- RNA, Messenger
- Tgfb1 protein, mouse
- Tissue Inhibitor of Metalloproteinases
- Transforming Growth Factor beta
- Transforming Growth Factor beta1
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Apoptosis
- Atrophy
- B-Lymphocytes
(pathology)
- Fibroblasts
(pathology)
- Fibrosis
- Kidney
(pathology)
- Matrix Metalloproteinase 2
(genetics)
- Matrix Metalloproteinase 9
(genetics)
- Mice
- Mice, Inbred Strains
- Mice, Mutant Strains
- Monocytes
(pathology)
- Nephritis, Hereditary
(pathology, physiopathology)
- RNA, Messenger
(analysis)
- T-Lymphocytes
(pathology)
- Tissue Inhibitor of Metalloproteinases
(genetics)
- Transforming Growth Factor beta
(genetics)
- Transforming Growth Factor beta1
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