Diabetes, Metabolic Syndrome and Obesity (Nov 2021)
RPS4Y1 Promotes High Glucose-Induced Endothelial Cell Apoptosis and Inflammation by Activation of the p38 MAPK Signaling
Abstract
Yuan Chen,1,* Yiheng Chen,2,* Chonghui Tang,3 Qian Zhao,1 Tailin Xu,1 Qi Kang,1 Bin Jiang,2 Li Zhang4 1Department of Endocrinology, The First People’s Hospital of Zunyi, Zunyi, Guizhou, 563000, People’s Republic of China; 2Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 315300, People’s Republic of China; 4Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li ZhangDepartment of Neurosurgery, China-Japan Friendship Hospital, No. 2 Yinghua East Road, District of Chaoyang, Beijing, 100029, People’s Republic of ChinaEmail [email protected]: Endothelial dysfunction is a key pathological basis for diabetes mellitus complications, including diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. This study aimed to reveal the functional role of ribosomal protein S4 Y-linked 1 (RPS4Y1) in endothelial dysfunction.Methods: Human umbilical vein endothelial cells (HUVECs) were subjected to high glucose. The expression of RPS4Y1 in cells was overexpressed or silenced by plasmid or siRNA transfection. MTT assay, flow cytometry, JC-1 probe, scratch test, tube formation, and ELISA were conducted to assess the effects of RPS4Y1 on cell. Western blot was performed to assay the downstream signaling of RPS4Y1. The inhibitors of p38, ERK, and Jnk were used to treat cells to validate the involvement of them in RPS4Y1-mediated endothelial dysfunction.Results: RPS4Y1 was upregulated in HUVECs in response to high glucose in both dose- and time-dependent manners. Overexpression of RPS4Y1 induced viability loss, apoptosis, and inflammation, but inhibited cell migration and tube formation. Silence of RPS4Y1 impacted these aspects in a contrary trend. The phosphorylation of p38 rather than ERK and Jnk was activated by RPS4Y1. In addition, the dysfunction of HUVECs mediated by RPS4Y1 was attenuated by SB203580 (a specific inhibitor of p38 signaling).Conclusion: The highly expressed RPS4Y1 in endothelial cells may contribute to high glucose-induced dysfunction through regulating p38 MAPK signaling. RPS4Y1 might be a potential therapeutic target for treating diabetes mellitus complications.Keywords: RPS4Y1, HUVEC, diabetes mellitus, high glucose, p38 MAPK signaling
