Npc1 gene mutation abnormally activates the classical Wnt signalling pathway in mouse kidneys and promotes renal fibrosis.

Niemann-Pick disease type C1 (NPC1) is a lysosomal lipid storage disease caused by NPC1 gene mutation. Our previous study found that, compared with wild-type (Npc1 +/+ ) mice, the renal volume and weight of Npc1 gene mutant (Npc1 -/- ) mice were significantly reduced. We speculate that Npc1 gene mutations may affect the basic structure of the kidneys of Npc1 -/- mice, and thus affect their function. Therefore, we randomly selected postnatal Day 28 (P28) and P56 Npc1 +/+ and Npc1 -/- mice, and observed the renal structure and pathological changes by haematoxylin-eosin staining. The level of renal fibrosis was detected by immunofluorescence histochemical techniques, and western blotting was used to detect the expression levels of apoptosis-related proteins and canonical Wnt signalling pathway related proteins. The results showed that compared with Npc1 +/+ mice, the kidneys of P28 and P56 Npc1 -/- mice underwent apoptosis and fibrosis; furthermore, there were obvious vacuoles in the cytoplasm of renal tubular epithelial cells of P56 Npc1 -/- mice, the cell bodies were loose and foam-like, and the canonical Wnt signalling pathway was abnormally activated. These results showed that Npc1 gene mutation can cause pathological changes in the kidneys of mice. As age increased, vacuoles developed in the cytoplasm of renal tubular epithelial cells, and apoptosis of renal cells, abnormal activation of the Wnt signalling pathway, and promotion of renal fibrosis increased.