1. Academic Validation
  2. TRIM27 contributes to glomerular endothelial cell injury in lupus nephritis by mediating the FoxO1 signaling pathway

TRIM27 contributes to glomerular endothelial cell injury in lupus nephritis by mediating the FoxO1 signaling pathway

  • Lab Invest. 2021 Aug;101(8):983-997. doi: 10.1038/s41374-021-00591-9.
Jinxi Liu  # 1 Jie Xu  # 1 Jie Huang 1 Cunyang Gu 1 Qingjuan Liu 1 Wei Zhang 1 Fan Gao 1 Yuexin Tian 1 Xinyan Miao 1 Zixuan Zhu 2 Baiyun Jia 2 Yu Tian 1 3 Lunbi Wu 1 Hang Zhao 1 Xiaojuan Feng 4 Shuxia Liu 5
Affiliations

Affiliations

  • 1 Department of Pathology; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University; Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China.
  • 2 Basic Medicine, Hebei Medical University, Shijiazhuang, China.
  • 3 Department of Rheumatology, The Second Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
  • 4 Department of Pathology; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University; Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China. [email protected].
  • 5 Department of Pathology; Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University; Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang, China. [email protected].
  • # Contributed equally.
Abstract

Tripartite motif-containing 27 (TRIM27) belongs to the triple motif (TRIM) protein family, which plays a role in a variety of biological activities. Our previous study showed that the TRIM27 protein was highly expressed in the glomerular endothelial cells of patients suffering from lupus nephritis (LN). However, whether TRIM27 is involved in the injury of glomerular endothelial cells in lupus nephritis remains to be clarified. Here, we detected the expression of the TRIM27 protein in glomerular endothelial cells in vivo and in vitro. In addition, the influence of TRIM27 knockdown on endothelial cell damage in MRL/lpr mice and cultured human renal glomerular endothelial cells (HRGECs) was explored. The results revealed that the expression of TRIM27 in endothelial cells was significantly enhanced in vivo and in vitro. Downregulating the expression of TRIM27 inhibited the breakdown of the glycocalyx and the injury of endothelial cells via the FoxO1 pathway. Moreover, HRGECs transfected with the WT-FoxO1 plasmid showed a reduction in impairment caused by LN plasma. Furthermore, suppression of the protein kinase B (Akt) pathway could attenuate damage by mediating the expression of TRIM27. Thus, the present study showed that TRIM27 participated in the injury of glomerular endothelial cells and served as a potential therapeutic target for the treatment of lupus nephritis.

Figures
Products