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The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension
Published on: May 17, 2024
Hepatocyte nuclear factor 1 and hypertensive nephropathy.
Renata I Dmitrieva1, Cruz A Hinojos, Eric Boerwinkle
1Institute of Molecular Medicine, University of Texas HSC at Houston, TX 77030, USA.
Hypertension (Dallas, Tex. : 1979)
|April 30, 2008
Summary
Hypertension leads to kidney damage in spontaneously hypertensive rats (SHR-A3) due to reduced antioxidant gene expression. This is linked to altered hepatocyte nuclear factor 1 (HNF1) activity, preceding kidney injury.
Area of Science:
- Nephrology
- Genetics
- Molecular Biology
Background:
- Hypertension in spontaneously hypertensive rats (SHR) is linked to renal redox stress.
- Nephropathy development in SHR-A3 may stem from an impaired capacity to mitigate redox stress compared to resistant SHR lines.
Purpose of the Study:
- To investigate the alterations in renal redox gene expression in distinct SHR lines before the onset of hypertensive renal injury.
- To identify the role of transcription factors, specifically hepatocyte nuclear factor 1 (HNF1), in regulating these gene expression changes.
Main Methods:
- Measured renal expression of redox genes in SHR-A3, SHR-B2, SHR-C, and Wistar-Kyoto (WKY) rats.
- Analyzed transcription factor matrices (HNF1) in the promoters of downregulated antioxidant genes.
- Examined the expression of genes comprising HNF1 (Tcf1, Tcf2, Dcoh).
Main Results:
- SHR-A3 exhibited profound alterations in redox gene expression, with 16 of 28 antioxidant genes downregulated before renal injury.
- HNF1 transcription factor binding sites were significantly more frequent in the promoters of downregulated antioxidant genes in SHR-A3.
- 35 non-redox renal genes regulated by HNF1 and HNF1 component genes (Tcf1, Tcf2, Dcoh) were also downregulated in SHR-A3 but not in resistant lines.
Conclusions:
- A significant change in transcriptional control by HNF1 precedes the emergence of hypertensive renal injury in SHR-A3.
- HNF1 dysregulation impacts both redox and other renal genes, contributing to nephropathy development.
- This study reveals a key molecular mechanism underlying hypertensive kidney disease in SHR.
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