Publication Name	World Journal of Diabetes
Manuscript ID	108101
Country	China

Category	Urology & Nephrology
Manuscript Type	Basic Study
Article Title	Hyperglycemia-induced overexpression of CREB3 L3 promotes epithelial-to-mesenchymal transition in bladder urothelial cells in diabetes mellitus
Manuscript Source	Unsolicited Manuscript
All Author List	Qing-Guo Wu, Ming-Jin Zhang, Yi-Bi Lan, Chun-Lei Ma and Wei-Jin Fu
Funding Agency and Grant Number	Funding Agency Grant Number GuangXi Natural Science Foundation 2024GXNSFAA010031
Corresponding Author	Wei-Jin Fu, Chief Physician, Department of Urology, The First Affiliated Hospital of GuangXi Medical University, No. 6 Shuangyong Road, Qinxiu District, Nanning 530022, Guangxi Zhuang Autonomous Region, China. fwjgxmu1978@163.com
Key Words	Diabetic cystopathy; Epithelial-mesenchymal transition; Hyperglycemia
Core Tip	Diabetic cystopathy (DCP), a debilitating complication of diabetes mellitus, involves hyperglycemia-driven bladder dysfunction. This study identified CREB3 L3 as a novel mediator of DCP pathogenesis. Chronic hyperglycemia induced CREB3 L3 overexpression in bladder urothelium, promoting C-reactive protein-dependent inflammation, epithelial-mesenchymal transition (EMT) and tight junction disruption. Silencing CREB3 L3 in SV-HUC-1 urothelial cells and a DCP rat model reversed EMT markers (downregulation of N-cadherin and upregulation of E-cadherin protein), restored barrier proteins (Occludin/Claudin1 protein), and attenuated bladder remodeling. These findings have established CREB3 L3 as a therapeutic target to preserve urothelial integrity and mitigate DCP progression.
Citation	Wu QG, Zhang MJ, Lan YB, Ma CL, Fu WJ. Hyperglycemia-induced overexpression of CREB3 L3 promotes epithelial-to-mesenchymal transition in bladder urothelial cells in diabetes mellitus. World J Diabetes 2025; In press

Received	2025-04-07 09:40
Peer-Review Started	2025-04-16 09:01
To Make the First Decision
Return for Revision	2025-04-24 02:46
Revised	2025-05-08 15:16
Second Decision	2025-06-17 02:48
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-07-02 09:11
Articles in Press	2025-07-02 09:11
Publication Fee Transferred	2025-05-10 16:23
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-9358 (online)
Open Access	Diabetic cystopathy (DCP), a debilitating complication of diabetes mellitus, involves hyperglycemia-driven bladder dysfunction. This study identified CREB3 L3 as a novel mediator of DCP pathogenesis. Chronic hyperglycemia induced CREB3 L3 overexpression in bladder urothelium, promoting C-reactive protein-dependent inflammation, epithelial-mesenchymal transition (EMT) and tight junction disruption. Silencing CREB3 L3 in SV-HUC-1 urothelial cells and a DCP rat model reversed EMT markers (downregulation of N-cadherin and upregulation of E-cadherin protein), restored barrier proteins (Occludin/Claudin1 protein), and attenuated bladder remodeling. These findings have established CREB3 L3 as a therapeutic target to preserve urothelial integrity and mitigate DCP progression.
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