Anna A. Brezgunova (1) (2), Nadezda V. Andrianova (2), Vasily A. Popkov (2) (3), Sergey Y. Tkachev (4) (5), Vasily N. Manskikh (2), Irina B. Pevzner (2) (3), Ljubava D. Zorova (2) (3), Peter S. Timashev (4) (5), Denis N. Silachev (2) (3), Dmitry B. Zorov (2) (3), Egor Y. Plotnikov (2) (3)
Biochimica et Biophysica Act (BBA) - Molecular Basis of Disease. Volume 1869, Issue 3 (March 2023). DOI: https://doi.org/10.1016/j.bbadis.2022.166622

Keywords

Kidney, experimental model, photo-induced damage, bengal rose, fibrosis, regeneration

Abstract

Acute Kidney injury (AKI) is a frequent pathology with a high mortality rate after even a single AKI episode and a great risk of chronic kidney disease (CKD) development. To get insight into mechanisms of the AKI pathogenesis, there is a need to develop diverse experimental models of the disease. Photothrombosis is a widely used method for inducing ischemia in the brain. In this study, for the first time, we described photothrombosis-induced kidney ischemia as an appropriate model of AKI and obtained comprehensive characteristics of the photothrombotic lesion using micro-computed tomography (micro-CT) and histological techniques. In the ischemic area, we observed destruction of tubules, the loss of brush border and nuclei, connective tissue fibers disorganization, leukocyte infiltration, and hyaline casts formation. In kidney tissue and urine, we revealed increased levels in markers of proliferation and injury. The explicit long-term consequence of photothrombosis-induced kidney ischemia was renal fibrosis. Thus, we establish a new low invasive experimental model of AKI, which provides a reproducible local ischemic injury lesion. We propose our model of photothrombosis-induced kidney ischemia as a useful approach for investigating AKI pathogenesis, studying the mechanisms of kidney regeneration, and development of therapy against AKI and CKD.

How Our Software Was Used

Micro-CT images were analyzed in Dragonfly in three ways: two- and three-dimensional visualization, kidney and lesion volume calculation, and gray value analysis of different parts of the organ.

Author Affiliation

(1) Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia
(2) A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia
(3) V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Moscow, Russia
(4) Institute for Regenerative Medicine, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
(5) World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia