Tohoku J. Exp. Med., 2023 November, 261(3)

Cell Division Control Protein 42 Facilitates Diabetic Retinopathy Progression by Activating the MEK/ERK Pathway

Hui Cao¹ and Changzheng Hou²

¹Department of Ophthalmology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China
²Department of Anesthesiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China

Cell division control protein 42 (CDC42) modulates insulin secretion and angiogenesis to participate in the pathology of diabetic complications and retinal vascular-associated diseases. This study intended to explore the role of CDC42 in the progression of diabetic retinopathy, and the underlying mechanism. Human retinal microvascular endothelial cells (hRMECs) were cultured in 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose; HG) medium, respectively. CDC42 overexpression plasmid and small interference RNA (oe-CDC42 and si-CDC42) or corresponding negative controls (oe-NC and si-NC) were transfected into hRMECs under HG. Then, platelet-activating factor C-16 (C16-PAF) (MEK/ERK pathway activator) was added to si-CDC42 or si-NC transfected hRMECs under HG. Our study showed that HG increased CDC42 mRNA and protein, cell viability, invasive cell count, branch points, and tube length but reduced cell apoptosis in hRMECs. CDC42 upregulation enhanced cell viability, invasive cell count, branch points, tube length, p-MEK, and p-ERK, but attenuated cell apoptosis. Downregulation of CDC42 exhibited opposite trends. In addition, C16-PAF also increased cell viability, invasive cell count, branch points, and tube length, p-MEK, and p-ERK, but retarded cell apoptosis. Notably, C16-PAF diminished the effect of CDC42 downregulation on the above-mentioned functions in hRMECs under HG. Conclusively, CDC42 promotes HG-induced hRMEC viability and invasion, as well as angiogenesis, but inhibits apoptosis by activating the MEK/ERK pathway, which may be responsible for the progression of diabetic retinopathy.

Key words —— angiogenesis; cell division control protein 42; cell viability and invasion; diabetic retinopathy; MEK/ERK pathway

© 2023 Tohoku University Medical Press

===============================

Tohoku J. Exp. Med., 2023 November, 261(3), 211-219.

*These two authors contributed equally to this work.

Correspondence: Hui Cao, Department of Ophthalmology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, No.161 Shaoshan South Road, Yuhua District, Changsha, Hunan 410013, China.

e-mail: chuangpujiuoc@163.com