Distinct sites of renal fibrosis in the Crim1 mutant mice arise from multiple cellular origins

Phua, Yu Leng, Martel, Nick, Pennisi, David J., Little, Melissa H. and Wilkinson, Lorine J. (2013) Distinct sites of renal fibrosis in the Crim1 mutant mice arise from multiple cellular origins. Journal of Pathology, 229 5: 685-696. doi:10.1002/path.4155


Author Phua, Yu Leng
Martel, Nick
Pennisi, David J.
Little, Melissa H.
Wilkinson, Lorine J.
Title Distinct sites of renal fibrosis in the Crim1 mutant mice arise from multiple cellular origins
Formatted title
Distinct sites of renal fibrosis in the Crim1 mutant mice arise from multiple cellular origins
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 1096-9896
0022-3417
Publication date 2013-04
Year available 2013
Sub-type Article (original research)
DOI 10.1002/path.4155
Volume 229
Issue 5
Start page 685
End page 696
Total pages 38
Place of publication West Sussex, United Kingdom
Publisher John Wiley & Sons
Collection year 2014
Language eng
Formatted abstract
Crim1 is a transmembrane protein which regulates the bioavailability of growth factors such as VEGFA. The Crim1KST264/KST264 hypomorphic mice develop renal disease characterised by glomerular cysts and loss of endothelial integrity, progressing to peritubular and pericystic fibrosis. The peritubular capillary endothelial cells display morphological changes as well as detachment from the basement membrane. In this study, gene expression profiling of CD31+ endothelial cells isolated from Crim1KST264/KST264 kidneys showed upregulation of transcripts associated with fibrosis (Col3a1, Loxl1), endothelial dysfunction (Abp1, Dcn, Lcn2), biomarkers of renal damage (Lcn2, Havcr1/Kim1) as well as evidence for a TGFβ1/TNF associated inflammatory process. To determine whether the aberrant endothelium may in part contribute to the fibrogenic process, Tie2Cre-DsRed lineage tracing was undertaken in the Crim1KST264/KST264 mice. Approximately 31% of de novo αSMA+ myofibroblasts detected within the tubulointerstitium were Tie2+DsRed+. However, 5.3% were F4/80+DsRed+, indicating a small population of myofibroblasts of monocytic rather than endothelial origin. In contrast, only 12% of myofibroblasts located around glomerular cysts were Tie2+DsRed+ with 7.7% being monocyte-derived (F4/80+DsRed+). Collectively, this model supports the involvement of endothelial cells/monocytes in fibrosis within the tubulointerstitium, but also the heterogeneity of the fibrotic process even within distinct regions of the same kidney.
Keyword Endothelial to mesenchymal transition
Endothelial cells
Monocytes
Glomerulus
Renal fibrosis
Renal inflammation
Crim1
Havcr1/Kim1
Collagen type III
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 17 Jan 2013, 14:43:04 EST by Susan Allen on behalf of Institute for Molecular Bioscience