期刊
JOURNAL OF PATHOLOGY
卷 227, 期 4, 页码 499-510出版社
WILEY-BLACKWELL
DOI: 10.1002/path.4036
关键词
obstructive nephropathy; functional obstruction; hydronephrosis; magnetic resonance imaging; Crim1; pyeloureteric peristalsis
资金
- UQIRTA
- UQRS
- Japan Society for the Promotion of Science [22390304]
- NHMRC [491060]
- Grants-in-Aid for Scientific Research [22390304] Funding Source: KAKEN
Crim1 hypomorphic (Crim1(KST264/KST264)) mice display progressive renal disease characterized by glomerular defects, leaky peritubular vasculature, and progressive interstitial fibrosis. Here we show that 27% of these mice also present with hydronephrosis, suggesting obstructive nephropathy. Dynamic magnetic resonance imaging using Magnevist showed fast development of hypo-intense signal in the kidneys of Crim1(KST264/KST264) mice, suggesting pooling of filtrate within the renal parenchyma. Rhodamine dextran (10 kDa) clearance was also delayed in Crim1(KST264/KST264) mice. Pyeloureteric peristalsis, while present, was less co-ordinated in Crim1(KST264/KST264) mice. However, isolated renal pelvis preparations suggest normal pelvic smooth muscle contractile responses. An analysis of maturation during the immediate postnatal period [postnatal day (P) 0-15] revealed defects in papillary extension in Crim1(KST264/KST264) mice. While Crim1 expression is weak in pelvic smooth muscle, strong expression is seen in the interstitium and loops of Henle of the extending papilla, commencing at the tip of the P1 papilla and disseminating throughout the papilla by P15. These results, as well as implicating Crim1 in papillary extension and pelvic smooth muscle contractility, highlight the previously unrecognized association between defects in papillary development and progression to chronic kidney disease later in life. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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