The Importance of Heterogeneous Nuclear Ribonucleoprotein K on Cytochrome P450 2D2 Gene Regulation: Its Binding Is Reduced in Dark Agouti Rats

2009 ◽  
Vol 37 (8) ◽  
pp. 1703-1710 ◽  
Author(s):  
Noriaki Sakai ◽  
Kentaro Q. Sakamoto ◽  
Shoichi Fujita ◽  
Mayumi Ishizuka
Keyword(s):  
Gene Regulation ◽  
Cytochrome P450 ◽  
Dark Agouti ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

scholarly journals Tubular Deficiency of Heterogeneous Nuclear Ribonucleoprotein F Elevates Systolic Blood Pressure and Induces Glycosuria in Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chao-Sheng Lo ◽  
Kana N. Miyata ◽  
Shuiling Zhao ◽  
Anindya Ghosh ◽  
Shiao-Ying Chang ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Interstitial Fibrosis ◽  
Sglt2 Inhibitor ◽  
Systemic Hypertension ◽  
Male And Female ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Elevated Systolic Blood Pressure ◽  
Nuclear Ribonucleoprotein ◽  
Heterogeneous Nuclear Ribonucleoprotein F

Abstract We reported previously that overexpression of heterogeneous nuclear ribonucleoprotein F (Hnrnpf) in renal proximal tubular cells (RPTCs) suppresses angiotensinogen (Agt) expression, and attenuates systemic hypertension and renal injury in diabetic Hnrnpf-transgenic (Tg) mice. We thus hypothesized that deletion of Hnrnpf in the renal proximal tubules (RPT) of mice would worsen systemic hypertension and kidney injury, perhaps revealing novel mechanism(s). Tubule-specific Hnrnpf knockout (KO) mice were generated by crossbreeding Pax8-Cre mice with floxed Hnrnpf mice on a C57BL/6 background. Both male and female KO mice exhibited elevated systolic blood pressure, increased urinary albumin/creatinine ratio, tubulo-interstitial fibrosis and glycosuria without changes in blood glucose or glomerular filtration rate compared with control littermates. However, glycosuria disappeared in male KO mice at the age of 12 weeks, while female KO mice had persistent glycosuria. Agt expression was elevated, whereas sodium-glucose co-transporter 2 (Sglt2) expression was down-regulated in RPTs of both male and female KO mice as compared to control littermates. In vitro, KO of HNRNPF in human RPTCs (HK-2) by CRISPR gRNA up-regulated AGT and down-regulated SGLT2 expression. The Sglt2 inhibitor canagliflozin treatment had no effect on Agt and Sglt2 expression in HK-2 and in RPTCs of wild-type mice but induced glycosuria. Our results demonstrate that Hnrnpf plays a role in the development of hypertension and glycosuria through modulation of renal Agt and Sglt2 expression in mice, respectively.

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