학술논문
The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression
Document Type
article
Author
Aya Tomita-Yagi; Natsuko Ozeki-Okuno; Noriko Watanabe-Uehara; Kazumi Komaki; Minato Umehara; Hiroko Sawada-Yamauchi; Atsushi Minamida; Yasuto Sunahara; Yayoi Matoba; Itaru Nakamura; Tomohiro Nakata; Kunihiro Nakai; Tomoharu Ida; Noriyuki Yamashita; Michitsugu Kamezaki; Yuhei Kirita; Takuya Taniguchi; Eiichi Konishi; Satoaki Matoba; Keiichi Tamagaki; Tetsuro Kusaba
Source
iScience, Vol 27, Iss 2, Pp 109020- (2024)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: The immense public health burden of diabetic kidney disease (DKD) has led to an increase in research on the pathophysiology of advanced DKD. The present study focused on the significance of proinflammatory vascular cell adhesion molecule 1 (VCAM1)+ tubules in DKD progression. A retrospective cohort study of DKD patients showed that the percentage of VCAM1+ tubules in kidney samples was correlated with poor renal outcomes. We established an advanced DKD model by partial resection of the kidneys of db/db mice and demonstrated that it closely resembled the human advanced DKD phenotype, with tissue hypoxia, tubular DNA damage, tissue inflammation, and high tubular VCAM1 expression. Luseogliflozin ameliorated tissue hypoxia and proinflammatory responses, including VCAM1+ expression, in tubules. These findings suggest the potential of tubular VCAM1 as a histological marker for poor DKD outcomes. SGLT2 inhibitors may attenuate tissue hypoxia and subsequent tissue inflammation in advanced DKD, thereby ameliorating tubular injury.