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Your search keyword '"Rui Zhang"' showing total 2 results
Start Over Author "Rui Zhang" Topic apoptosis Publisher american diabetes association
2 results on '"Rui Zhang"'

1. 517-P: Communication from Tubular Epithelial Cells to Podocytes through Bim/NFAT2 Pathway

Author

Shan Jiang, Chunmei Xu, Yiqian Xing, Rui Zhang, Zhiwei Zou, Lin Liao, Xiaojun Zhou, Jianjun Dong, Qian Zhang, Xue Shen, and Tianyue Xie

Subjects
Gene knockdown, Endocrinology, Diabetes and Metabolism, T cell, NFAT, Biology, medicine.disease, Filamentous actin, Podocyte, Diabetic nephropathy, medicine.anatomical_structure, Apoptosis, Internal Medicine, medicine, Cancer research, Synaptopodin
Abstract

Background: Our previous research revealed that the apoptosis of proximal tubular epithelial cells (PTECs) occupied a vital position in the early change of diabetic nephropathy (DN) and Bcl-interacting mediator (Bim) was the key factor to be involved in it. Whereas, Bim could also control T cell activation and play a specific regulatory role in other aspects besides inducing cell apoptosis. Changes of podocytes are classic hallmarks of the lesions of DN. Here, the study aims to investigate the specific influence of PTECs which have been damaged on the podocyte injury. Methods: Bim expression in PTECs was modulated, and subsequently podocyte cytoskeleton was determined at different points of time (24, 48, 72 hours) by building transwell co-culture system under high glucose (40mmol/l HG). Results: HG exposure for 48 hours induced the significant changes in podocyte cytoskeleton accompanied with high expression of Bim in PTECs. When co-cultured with PTECs, exacerbated filamentous actin (F-actin) rearrangement and markedly reduced synaptopodin level in podocytes were found compared with single cultured podocytes under HG. Gene knockdown of Bim in PTECs ameliorated above abnormalities in podocytes. Further screening for NFAT subtypes, the key downstream factors of Bim, found that NFAT2 level in PTECs was obviously decreased when suppressing Bim expression. Upregulating NFAT2 disrupted beneficial effects on podocyte F-actin arrangement which was achieved by inhibiting Bim in PTECs. Conclusion: Our preliminary data have indicated that the apoptosis of PTECs mediates the early lesion of DN. It seemed corroborative that there exists crosstalk between PTECs and podocytes; Bim, the pivotal factor related to apoptosis of PTECs participates in the crosstalk by promoting NFAT2 activation, then contributes to injury of podocyte cytoskeleton, emphasizing the role of Bim/NFAT2 pathway in the control of early DN progression from tubular lesions to glomerular abnormalities. Disclosure C. Xu: None. X. Zhou: None. X. Shen: None. S. Jiang: None. T. Xie: None. Z. Zou: None. Q. Zhang: None. R. Zhang: None. Y. Xing: None. L. Liao: None. J. Dong: None. Funding National Natural Science Foundation of China (81570742, 81670757, 81770822, 81800732); Shandong Provincial Natural Science Foundation of China (ZR2017LH025); Shandong Provincial Medicine and Health Science and Technology Development Program (2017WS461)

Published
2019

2. An Essential Role of NRF2 in Diabetic Wound Healing.

Author

Min Long, de la Vega, Montserrat Rojo, Qing Wen, Bharara, Manish, Tao Jiang, Rui Zhang, Shiwen Zhou, Wong, Pak K., Wondrak, Georg T., Hongting Zheng, Donna D. Zhang, Long, Min, Rojo de la Vega, Montserrat, Wen, Qing, Jiang, Tao, Zhang, Rui, Zhou, Shiwen, Zheng, Hongting, and Zhang, Donna D

Subjects
SKIN ulcers, TREATMENT of diabetes, WOUND healing, OXIDATIVE stress, NUCLEAR factor of activated T-cells, PROTEIN metabolism, TYPE 2 diabetes complications, REACTIVE oxygen species, ANIMAL experimentation, APOPTOSIS, CELL physiology, DIABETES, GROWTH factors, IMMUNOBLOTTING, IMMUNOHISTOCHEMISTRY, TYPE 1 diabetes, KERATINOCYTES, MICE, TYPE 2 diabetes, PROTEINS, PROTEOLYTIC enzymes, RESEARCH funding, SKIN, DIABETIC foot, CASE-control method, DISEASE complications
Abstract

The high mortality and disability of diabetic nonhealing skin ulcers create an urgent need for the development of more efficacious strategies targeting diabetic wound healing. In the current study, using human clinical specimens, we show that perilesional skin tissues from patients with diabetes are under more severe oxidative stress and display higher activation of the nuclear factor-E2-related factor 2 (NRF2)-mediated antioxidant response than perilesional skin tissues from normoglycemic patients. In a streptozotocin-induced diabetes mouse model, Nrf2(-/-) mice have delayed wound closure rates compared with Nrf2(+/+) mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis. More importantly, pharmacological activation of the NRF2 pathway significantly improves diabetic wound healing. In vitro experiments in human immortalized keratinocyte cells confirm that NRF2 contributes to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, and increasing the expression of TGF-β1 and lowering MMP9 under high-glucose conditions. This study indicates an essential role for NRF2 in diabetic wound healing and the therapeutic benefits of activating NRF2 in this disease, laying the foundation for future clinical trials using NRF2 activators in treating diabetic skin ulcers. [ABSTRACT FROM AUTHOR]

Published
2016
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