AUTHOR=Wu Chao , Yan Fang , Li Min , Tu Yimin , Guo Ziyu , Chen Yufei , Wu Yaxin , Li Qing , Yu Changan , Fu Yi , Wu Meihui , Kong Wei , Gao Yanxiang , Li Xiaowei , Zheng Jingang TITLE=Whole-Mount Kidney Clearing and Visualization Reveal Renal Sympathetic Hyperinnervation in Heart Failure Mice JOURNAL=Frontiers in Physiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.696286 DOI=10.3389/fphys.2021.696286 ISSN=1664-042X ABSTRACT=

Developing a three-dimensional (3D) visualization of the kidney at the whole-mount scale is challenging. In the present study, we optimized mouse whole-mount kidney clearing, which improved the transparency ratio to over 90% based on organ-specific perfusion (OSP)-clear, unobstructed brain imaging cocktails and computational analysis (CUBIC). The optimized OSP-CUBIC-compatible 3D immunostaining and imaging simultaneously visualized the high-resolution 3D structure of the whole-mount renal microvascular, glomerulus, and accompanying wrapped traveling sympathetic nerves in mice. A mouse model of pressure overload-induced heart failure (HF) was then established by minimally invasive transverse aortic constriction (MTAC). Further 3D quantification revealed renal sympathetic hyperinnervation (6.80 ± 1.04% vs. 3.73 ± 0.60%, P < 0.05) in mice with HF. In conclusion, this newly developed whole-organ tissue clearing and imaging system provides comprehensive information at the whole-mount scale and has great potential for kidney research. Our data suggest that renal sympathetic hyperinnervation is involved in HF associated with renal dysfunction.