Speciﬁcity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells - an updated review

Sep 28, 2026

Diabetic kidney disease (DKD) is a major diabetic microvascular complication marked by persistent proteinuria, reduced glomerular filtration rate, and progressive pathological changes leading to end-stage renal disease. Renal endothelial cell homeostasis supports glomerular structure and function through anti-inflammatory and antithrombotic control while limiting fibrosis. Although intrinsic renal injury is widely studied, the distinct roles of glomerular endothelial cells in endothelial dysfunction and their communication with neighboring cells are less defined. This review synthesizes evidence on glomerular endothelial cell phenotypic heterogeneity, early glycocalyx damage, late fibrosis, and dynamic crosstalk with podocytes, mesangial cells, and tubular epithelial cells, plus endothelial-targeted therapeutic strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Diabetic kidney disease and early endothelial injury

Mechanisms of hyperglycemia-induced endothelial dysfunction

Molecular regulation, inflammation, oxidative stress, and adhesion molecules

Angiogenesis dysregulation in DKD

TYPE Review PUBLISHED 17 December 2025 DOI 10.3389/fendo.2025.1742296 OPEN ACCESS EDITED BY Swaran J. S. Flora, National Institute of Pharmaceutical Education and Research, India REVIEWED BY Raushan Kumar, ERA ’s Lucknow Medical College, India Soumik Das, Vellore Institute of Technology, India *CORRESPONDENCE Min Li [min_li2025@163.com](min_li2025@163.com) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 08 November 2025 REVISED 28 November 2025 ACCEPTED 05 December 2025 PUBLISHED 17 December 2025 CITATION Li J, Zhang Y, Sun X, Guan H, Wang J, Zhao S, Tian C, Han M, Ma K and Li M (2025) Speciﬁcity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review. Front. Endocrinol. 16:1742296 . doi: 10.3389/fendo.2025.1742296 COPYRIGHT © 2025 Li, Zhang, Sun, Guan, Wang, Zhao, Tian, Han, Ma and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Speciﬁcity of endothelial cells in endothelial dysfunction of diabetic kidney disease and their crosstalk with neighboring cells: an updated review Jiarui Li 1†, Yue Zhang 1†, Xiao Sun 2†, Huifang Guan 1, Jingshuo Wang 3, Shuang Zhao 1, Chuanxi Tian 2, Mingda Han 1, Kaile Ma 4 and Min Li 4* 1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China, 2Guang’ anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China, 3The Afﬁliated Hospital to Changchun University of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China, 4 Research Laboratory of Molecular Biology, Guang’anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China Diabetic kidney disease (DKD), a major microvascular complication of diabetes, is characterized by persistent proteinuria, a declining glomerular ﬁltration rate (GFR), and distinctive pathological alterations, often progressing to end-stage renal disease (ESRD) . Renal endothelial cells homeostasis is essential for maintaining glomerular architecture and function, sustaining an antiinﬂammatory and antithrombotic environment, and preventing ﬁbrosis. Although injury to intrinsic renal cells has been widely studied, the distinct contribution of glomerular endothelial cells (GECs) to endothelial dysfunction and their crosstalk with neighboring cells remain poorly deﬁned. Crosstalk between renal cells is critical for integrity of the glomerular ﬁltration barrier (GFB) and overall renal homeostasis. This review provides an updated and systematic overview of the distinct roles of GECs in DKD, encompassing their phenotypic heterogeneity, early glycocalyx damage with increased vascular permeability, and late-stage renal ﬁbrosis. It further elaborates on the dynamic interactions between GECs and podocytes, mesangial cells (MCs), and tubular epithelial cells (TECs) . Additionally, we summarize therapeutic strategies targeting endothelial function in DKD, including direct anti-hyperglycemic interventions, non-glycemic interventions, and approaches focused on endothelial injury biomarkers. In summary, this review highlights the distinct and underappreciated role of endothelial cells in DKD, emphasizing their therapeutic potential as a primary target. KEYWORDS cell communication, DKD, endothelial dysfunction, glomerular endothelial cells, mesangial cells, podocytes, tubular epithelial cells Frontiers in Endocrinology 01 [frontiersin.org](frontiersin.org) 1 Introduction Diabetic kidney disease (DKD) is one of

FAQs

What is the role of glomerular endothelial cells in DKD?

Glomerular endothelial cells maintain glomerular architecture and homeostasis and are vulnerable to hyperglycemia and circulating metabolites. Their dysfunction contributes to DKD initiation and progression.

How does endothelial glycocalyx damage relate to DKD?

Endothelial surface layer degradation is highlighted as an early marker of diabetic microvascular injury, associated with increased vascular permeability and downstream pathological changes.

Which neighboring cell types does the review emphasize in endothelial crosstalk?

The review focuses on dynamic interactions between glomerular endothelial cells and podocytes, mesangial cells, and tubular epithelial cells to explain disease progression and barrier integrity changes.

Sep 28, 2026

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