Abstract: PO2136
Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy
Session Information
- Mechanisms of Kidney and Vascular Disease
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1403 Hypertension and CVD: Mechanisms
Authors
- Bae, Eunjin, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam-do, Korea (the Republic of)
- Yu, Mi-yeon, Hanyang University Guri Hospital, Guri, Korea (the Republic of)
- Kim, Ji Eun, Korea University Guro Hospital, Seoul, Korea (the Republic of)
- Yoo, Kyung Don, Ulsan University Hospital, Ulsan, Korea (the Republic of)
- Moon, Jong joo, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Park, Dong Jun, Gyeongsang National University Changwon Hospital, Changwon, Gyeongsangnam-do, Korea (the Republic of)
- Kim, Yon Su, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Yang, Seung Hee, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
Background
Kruppel-like factor 2 (KLF2) is a transcription factor, which regulates endothelial cell metabolism. KLF2 plays a role in maintaining normal vascular integrity by proinflammatory, anti-thrombotic, anti-angiogenic effects in endothelial cells. Endothelial dysfunction is associated with hypertension, and is a predictor of atherosclerosis development and cardiovascular events. Also, it is commonly observed in chronic kidney disease (CKD). The association between glomerular endothelial cell damage in diabetic nephropathy of KLF2 has been studied, but not in hypertensive nephropathy. Here, we present a role of KLF2 in hypertensive nephropathy.
Methods
Human primary glomerular endothelial cells were harvested and cultured under various duration, pressure condition by a rotational force device for mimic hypertensive nephropathy. We established the appropriate culture environment by confirming the pressure and survival rate applied to endothelial cells according to rotational force and evaluate the mRNA expression of α-smooth muscle actin (αSMA), KLF2 and KLF4. To induce hypertensive nephropathy in rat, 5/6 nephrectomy was done and kidney injury marker, blood pressure, KLF2 expression were evaluated. And we evaluated the KLF2 expression in hypertensive nephropathy patients’ biopsied kidney tissue.
Results
The survival rate of human primary glomerular endothelial cells was maintained at a pressure of up to 4mmHg and decreased from above. After the application of 4mmHg pressure for 48hr in human primary glomerular endothelial cells, expression of KLF2 mRNA was decreased, while αSMA mRNA was increased and KLF4 mRNA was similar compared to control. 5/6 nephrectomy in rats resulted in increased blood pressure, decreased kidney function, as well as decreased KLF2 expression of glomerular endothelial cells. In addition, the expression of KLF2 in biopsied kidney tissue of hypertensive nephropathy patients was lower than that of normal kidney tissue.
Conclusion
We found that KLF2 expression of glomerular endothelial cells was reduced in both in vivo and in vitro models of hypertensive nephropathy. These findings suggest a new role for KLF2 in hypertensive nephropathy, which may be the basis for the development of new therapeutics.
Funding
- Government Support - Non-U.S.