The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression

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

doi:10.1016/j.isci.2024.109020

The importance of proinflammatory failed-repair tubular epithelia as a predictor of diabetic kidney disease progression

iScience. 2024 Jan 26;27(2):109020. doi: 10.1016/j.isci.2024.109020. eCollection 2024 Feb 16.

Authors

Aya Tomita-Yagi¹, Natsuko Ozeki-Okuno¹, Noriko Watanabe-Uehara¹, Kazumi Komaki¹, Minato Umehara¹, Hiroko Sawada-Yamauchi¹, Atsushi Minamida¹, Yasuto Sunahara¹, Yayoi Matoba¹, Itaru Nakamura¹, Tomohiro Nakata¹, Kunihiro Nakai¹, Tomoharu Ida¹, Noriyuki Yamashita¹, Michitsugu Kamezaki¹, Yuhei Kirita¹, Takuya Taniguchi², Eiichi Konishi³, Satoaki Matoba², Keiichi Tamagaki¹, Tetsuro Kusaba¹

Affiliations

¹ Department of Nephrology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
² Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
³ Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Abstract

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.

Keywords: Biological sciences; Health sciences; Internal medicine; Medical specialty; Medicine; Natural sciences; Nephrology; Pharmacology; Physiology.