Piperazine ferulate prevents high‑glucose‑induced filtration barrier injury of glomerular endothelial cells

Yang,Yong-Yu; Chen,Zhuo; Yang,Xi-Ding; Deng,Rong-Rong; Shi,Ling-Xing; Yao,Liang-Yuan; Xiang,Da-Xiong

doi:10.3892/etm.2021.10607

Piperazine ferulate prevents high‑glucose‑induced filtration barrier injury of glomerular endothelial cells

Authors:
- Yong-Yu Yang
- Zhuo Chen
- Xi-Ding Yang
- Rong-Rong Deng
- Ling-Xing Shi
- Liang-Yuan Yao
- Da-Xiong Xiang
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Affiliations: Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Geriatrics, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China, Department of Pharmacology, Changsha Medical University, Changsha, Hunan 410219, P.R. China, Hunan Qianjin Xiangjiang Pharmaceutical Industry Co., Ltd., Zhuzhou, Hunan 412000, P.R. China
Published online on: August 13, 2021 https://doi.org/10.3892/etm.2021.10607
Article Number: 1175
Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Filtration barrier injury induced by high glucose (HG) levels leads to the development of diabetic nephropathy. The endothelial glycocalyx plays a critical role in glomerular barrier function. In the present study, the effects of piperazine ferulate (PF) on HG‑induced filtration barrier injury of glomerular endothelial cells (GEnCs) were investigated and the underlying mechanism was assessed. Immunofluorescence was used to observe the distribution of the glycocalyx as well as the expression levels of syndecan‑1 and Zonula occludens‑1 (ZO‑1). Endothelial permeability assays were performed to assess the effects of PF on the integrity of the filtration barrier. Protein and mRNA expression levels were measured by western blotting and reverse transcription‑quantitative PCR analyses, respectively. In vitro experiments revealed that adenosine monophosphate‑activated protein kinase (AMPK) mediated HG‑induced glycocalyx degradation and endothelial barrier injury. PF inhibited the HG‑induced endothelial barrier injury and restored the expression levels of heparanase‑1 (Hpa‑1), ZO‑1 and occludin‑1 by AMPK. In vivo assays demonstrated that PF reduced the expression levels of Hpa‑1, increased the expression levels of ZO‑1 and attenuated glycocalyx degradation in the glomerulus. These data suggested that PF attenuated HG‑induced filtration barrier injury of GEnC by regulating AMPK expression.

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