Qing Zhu, Ph.D.
- Huazhong Agricultural University, China, 2008
- The goal of my research is to study the renal molecular mechanisms of salt-sensitive hypertension and related kidney injuries, which may ultimately lead to discovery of novel therapeutic targets of these diseases. Current projects are designed to study the roles of microRNA regulation of PHD2/HIF-1alpha mediated gene activation in the controls of renal Na+ handling and blood pressure.
MicroRNA-429 in the renal medulla and salt sensitivity of blood pressure:
HIF prolyl-hydroxylase 2 (PHD2) is an enzyme to promote the degradation of transcription factor hypoxia inducible factor (HIF)-1a. We have previously shown that high salt intake reduced PHD2 mRNA levels in the renal medulla, which consequently induced HIF-1alpha-mediated activation of anti-hypertensive genes. This PHD2/HIF-1alpha-mediated molecular adaptation in the renal medulla is important for the kidneys to remove extra Na+ loading and maintain normal blood pressure under high salt intake. Our preliminary studies showed that high salt diet enhanced the degradation of PHD2 mRNA in the renal medulla and that microRNA miR-429 was probably the upstream mediator for high salt-induced enhancement of PHD2 mRNA decay. The hypothesis to be tested is that miR-429 regulation of PHD2/HIF-1alpha-mediated activation of anti-hypertensive genes in the renal medulla contributes to renal salt adaptation and participates in the controls of renal Na+ handling and blood pressure. A series of cellular, molecular and whole animal experimental approaches are used to test this hypothesis, such as Western blot analysis, real time PCR, RNA interference, gene overexpression, in vivo molecular imaging, and whole animal monitoring of arterial pressure and renal functions.
Several animal and cell model systems have been used such as Dahl salt sensitive hypertensive rats, SS-13BN consomic rats, renal medullary interstitial cells, renal tubular cells and glomerular mesangial cells. Many advanced approaches are utilized including telemetry blood pressure recording, Laser-Doppler blood flowmeter, servo-control of renal perfusion pressure, in vivo molecular imaging, ESR spectrometry, immunohistochemistry, fluorescent microscopic imaging, confocal microscopy, real-time PCR, in vivo gene manipulation in the kidneys, etc.
Zhu Q, Hu J, Han WQ, Zhang F, Li PL, Wang Z, Li N. (2014) Silencing of HIF prolyl-hydroxylase 2 gene in the renal medulla attenuated salt-sensitive hypertension in Dahl S Rats. Am J Hypertens. 27(1):107-13.
Wang Z*, Zhu Q*(joint first author), Li PL, Dhaduk R, Zhang F, Gerl T, Li N. (2014) Silencing of Hypoxia Inducible Factor-1α Gene Attenuated Chronic Ischemic Renal Injury in Two-Kidney One-Clip Rats. Am J Physiol Renal Physiol. 306(10):F1236-42.
Hu J, Zhu Q, Xia M, Guo T, Wang Z, Li PL, Han WQ, Yi F, Li N. (2014) Transplantation of mesenchymal stem cells into the renal medulla attenuated salt-sensitive hypertension in Dahl S rat. J Mol Med. Epub ahead of print.
Han WQ, Zhu Q, Hu J, Li PL, Zhang F, Li N. (2013) Hypoxia-inducible factor prolyl-hydroxylase-2 mediates transforming growth factor beta 1-induced epithelial-mesenchymal transition in renal tubular cells. Biochim Biophys Acta. (BBA-Molecular cell research) 1833(6):1454-62.
Zhu Q, Wang Z, Xia M, Zhang F, Li PL, Li N. (2012) Overexpression of HIF-1α transgene in the renal medulla attenuated salt sensitive hypertension in Dahl S rats. Biochim Biophys Acta. (BBA-Molecular Basis of Disease) 1822(6):936-41.
Zhu Q, Liu M, Han WQ, Li PL, Wang Z, Li N. (2012) Overexpression of HIF prolyl-hydoxylase-2 transgene in the renal medulla induced a salt-sensitive hypertension. J Cell Mol Med. 16(11):2701-7.
Zhu Q, Wang Z, Xia M, Li PL, Van Tassell BW, Abbate A, Dhaduk R, Li N. (2011) Silencing of hypoxia-inducible factor-1αgene attenuated angiotensin II-induced renal injury in Sprague-Dawley rats. 58(4):657-64.
Zhu Q, Xia M, Wang Z, Li PL, Li N. (2011) A novel lipid natriuretic factor in the renal medulla: sphingosine-1-phosphate. Am J Physiol Renal Physiol. 301(1):F35-41.