Lack of Collagen XVIII/Endostatin Exacerbates Immune-Mediated Glomerulonephritis
| Autor: | Raghu Kalluri, Makoto Ogawa, Takashi Okude, Ikumi Sato, Yuki Hamano, Shiro Ueda, Ryota Kimura, Ryota Shirai, Osamu Yokosuka, Yoshihiko Ueda |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Anti-Glomerular Basement Membrane Disease Molecular Sequence Data macromolecular substances Biology urologic and male genital diseases Basement Membrane Extracellular matrix Mice Glomerulonephritis medicine Collagen Type XVIII Animals Amino Acid Sequence Basement membrane urogenital system Glomerular basement membrane Bowman Capsule Complement C3 General Medicine medicine.disease Endostatins Mice Inbred C57BL Vascular endothelial growth factor A Basic Research medicine.anatomical_structure Nephrology Immunoglobulin G Immunology cardiovascular system Female Rabbits Endostatin |
| Zdroj: | Journal of the American Society of Nephrology. 21:1445-1455 |
| ISSN: | 1046-6673 |
| Popis: | Collagen XVIII is a component of the highly specialized extracellular matrix associated with basement membranes of epithelia and endothelia. In the normal kidney, collagen XVIII is distributed throughout glomerular and tubular basement membranes, mesangial matrix, and Bowman's capsule. Proteolytic cleavage within its C-terminal domain releases the fragment endostatin, which has antiangiogenic properties. Because damage to the glomerular basement membrane (GBM) accompanies immune-mediated renal injury, we investigated the role of collagen XVIII/endostatin in this disorder. We induced anti-GBM glomerulonephritis in collagen XVIII alpha1-null and wild-type mice and compared the resulting matrix accumulation, inflammation, and capillary rarefaction. Anti-GBM disease upregulated collagen XVIII/endostatin expression within the GBM and Bowman's capsule of wild-type mice. Collagen XVIII/endostatin-deficient mice developed more severe glomerular and tubulointerstitial injury than wild-type mice. Collagen XVIII/endostatin deficiency altered matrix remodeling, enhanced the inflammatory response, and promoted capillary rarefaction and vascular endothelial cell damage, but did not affect endothelial proliferation. Supplementing collagen XVIII-deficient mice with exogenous endostatin did not affect the progression of anti-GBM disease. Taken together, these results suggest that collagen XVIII/endostatin preserves the integrity of the extracellular matrix and capillaries in the kidney, protecting against progressive glomerulonephritis. |
| Databáze: | OpenAIRE |
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