DLL1 promotes diabetic cataract progression by driving epithelial-mesenchymal transition (EMT) via activation of the Notch signaling pathway.

Authors

Yuanyuan Wang, Jiquan Wen, Tingting Zhu, Xiangming Zha, Chengcheng Fang, Zhen Li, Lijun Shen, Tingjun Xu

Published in

Biochimica et biophysica acta. Molecular cell research. Pages 120233. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

Diabetic cataracts (DCs) are a major vision-threatening complication of diabetes mellitus; however, their molecular mechanisms remain incompletely understood. The present study aimed to investigate the role of the Notch ligand δ-like ligand 1 (DLL1) in the pathogenesis of DCs. Immunohistochemical analysis revealed elevated DLL1 expression in anterior lens capsule tissues from patients with DCs compared with patients with age-related cataracts. In vitro, high-glucose treatment combined with TGF-β2 treatment induced epithelial-mesenchymal transition (EMT) in human lens epithelial cells (HLEB3), and this was accompanied by increased DLL1 expression. Knockdown of DLL1 significantly suppressed TGF-β2-induced cell proliferation, migration and EMT, as evidenced by restored E-cadherin levels and reduced fibronectin and vimentin levels. Furthermore, the effects of DLL1 knockdown were enhanced by pharmacological inhibition of Notch signaling using N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), confirming that DLL1 exerted its effects via the Notch pathway. In a streptozotocin-induced diabetic rat model, intravitreal administration of DLL1 small interfering RNA markedly attenuated lens opacity progression, improved lens histo-architecture, and downregulated the expression levels of EMT markers and Notch downstream targets (hes family bHLH transcription factor 1 and hes related family bHLH transcription factor with YRPW motif 1). Collectively, these findings demonstrated that DLL1 promoted DC progression by driving EMT via activation of the Notch signaling pathway. Therefore, targeting DLL1-mediated Notch signaling may potentially play a role in delaying or preventing DCs, although further studies are needed.

PMID:
42854987
Bibliographic data and abstract were imported from PubMed on 10 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.