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Thrombomodulin activation driven by LXR agonist attenuates renal injury in diabetic nephropathy

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机构： [1]Renal Division and Institute of Nephrology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China. [2]Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales Australia, Newtown, NSW, Australia. [3]Department of Renal Medicine, Concord Repatriation General Hospital, Concord Clinical School, University of Sydney, Camperdown, NSW, Australia. [4]Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia. [5]Internal Medicine, Louisiana State University Health Science at Shreveport, Shreveport, LA, United States. [6]The Faculty of Health Sciences and Medicine, Bond University, Gold Coast, QLD, Australia.

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关键词： liver X receptor thrombomodulin factor XIII-A inflammation diabetic nephropathy

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Inflammation and thrombosis are recognized as interrelated biological processes. Both thrombomodulin (TM) and factor XIII-A (FXIII-A) are involved in inflammation and coagulation process. However, their role in the pathogenesis of diabetic nephropathy (DN) remains unclear. In vitro study, the liver X receptor (LXR) agonist T0901317 can up-regulate the expression of TM in glomerular endothelial cells. Now we evaluated the interaction between TM activation and FXIII-A and their effects against renal injury.We first evaluated the serum levels of FXIII-A and TM and the expression of TM, LXR-α and FXIII-A in renal tissues of patients with biopsy-proven DN. We then analyzed the expression of TM, LXR-α and FXIII-A in renal tissues of db/db DN mice after upregulating TM expression via T0901317 or downregulating its expression via transfection of TM shRNA-loaded adenovirus. We also investigated the serum levels of Tumor necrosis factor (TNF)-α, Interleukin (IL)-6, creatinine, and urinary microalbumin level in db/db mice.Our study showed that elevations in serum levels of FXIII-A positively correlated to the serum levels of TM and were also associated with end-stage kidney disease in patients with DN. The number of TM+ cells in the renal tissues of patients with DN negatively correlated with the number of FXIII-A+ cells and positively correlated with the number of LXR-α+ cells and estimated glomerular filtration rate (eGFR), whereas the number of FXIII-A+ cells negatively correlated with the eGFR.Thrombomodulin activation with T0901317 downregulated FXIII-A expression in the kidney tissue and alleviated renal injury in db/db mice.Copyright © 2023 Wang, Wu, Wang, Wu, Luo, Zhao, Chen, Li and Ding.

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出版当年[2023]版：

大类 | 3 区医学

小类 | 3 区医学：内科

最新[2023]版：

大类 | 3 区医学

小类 | 3 区医学：内科

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出版当年[2023]版：

Q1 MEDICINE, GENERAL & INTERNAL

最新[2023]版：

Q1 MEDICINE, GENERAL & INTERNAL

影响因子： 3.1 最新[2023版] 3.4 最新五年平均 3.1 出版当年[2023版] 3.4 出版当年五年平均 3.9 出版前一年[2022版]

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第一作者机构： [1]Renal Division and Institute of Nephrology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

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通讯作者：

通讯机构： [2]Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales Australia, Newtown, NSW, Australia. [3]Department of Renal Medicine, Concord Repatriation General Hospital, Concord Clinical School, University of Sydney, Camperdown, NSW, Australia. [4]Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.

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Thrombomodulin activation driven by LXR agonist attenuates renal injury in diabetic nephropathy

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