Abstract
High resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to differentially reflect the altered microvasculature of renal TI lesions and/or glomerulopathy demonstrated these image features can be used to differentiate the disease status and the possible cause therefore qualified as image markers. These 3D imaging markers were further correlated with the histopathology and renal microvessel-based molecular study using antibodies against vascular endothelial cells (CD31), the connective tissue growth factor or the vascular endothelial growth factor. We also found that these 3D imaging markers individually characterize the development of renal TI lesions or glomerulopathy, quantitative and integrated use of all of them provide more information for differentiating the two renal conditions. Our findings thus establish a practical strategy to characterize the CKD-associated renal injuries by the microangiography-based 3D imaging and highlight the impact of dysfunctional microvasculature as a whole on the pathogenesis of the renal lesions.
Highlights
Chronic kidney disease (CKD) is a worldwide health issue
We successfully identified a number of 3D imaging markers characteristic to the altered microvessels in the mouse kidneys
We explored the potential implications of these markers in renal TI lesion and glomerulopathy using two mouse ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS) models of human chronic kidney disease (CKD) by comparing them with renal histopathology features and the results of renal microvessel-based molecular analysis
Summary
In spite of the high prevalence and incidence[1,2,3], the pathogenic mechanisms underlying the development and progression of CKD, their relation with the alteration of renal microvasculature, remain unclear. Angiogenic cytokines, such as connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF), are involved in tissue repair, and other essential biological functions, including vascular changes and fibrosis in CKD37, 38 Both proteins are highly expressed in the renal lesions of CKD patients and have been shown to play a pathogenic role in this group of renal disorders. These two proteins are required for the establishment of the microvasculature and the regulation of angiogenesis[39, 40]
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