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Related Experiment Videos

Human renin gene sequence, gene regulation and prorenin processing.

B J Morris, D F Cantanzaro, J Hardman

    Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension
    |December 1, 1984
    PubMed
    Summary

    Researchers sequenced human renin DNA, revealing gene structure and regulatory elements. This explains how renin is processed and activates angiotensinogen, with mouse studies showing differential gene expression.

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    Area of Science:

    • Molecular Biology
    • Genetics
    • Biochemistry

    Background:

    • The renin-angiotensin system plays a crucial role in blood pressure regulation.
    • Understanding the structure and regulation of the renin gene is essential for comprehending its physiological functions.

    Purpose of the Study:

    • To identify and sequence the human gene coding for renin.
    • To investigate the regulatory mechanisms of the renin gene.
    • To analyze the structural features of human preprorenin and renin.

    Main Methods:

    • DNA sequencing of the human renin gene, including upstream regulatory regions.
    • Prediction of amino acid sequences and processing sites of human preprorenin.
    • Analysis of the structural characteristics of human renin.

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  • Quantification of renin activity and mRNA in mouse models.
  • Hormonal and pharmacological manipulation to study gene expression.

    • Main Results:

    • The human renin gene comprises 10 exons and spans 12,000 base pairs, with introns interrupting the coding sequence for a 1500 nucleotide mRNA.
    • Predicted amino acid sequences revealed potential cleavage sites in the pro region, explaining activation by trypsin and pepsin.
    • Human renin possesses structural features, such as leucine at position 224, crucial for its specific hydrolysis of angiotensinogen.
    • In mice, sodium depletion, captopril, and spironolactone increased Ren-1 expression in the kidney.
    • The duplicated mouse Ren-2 gene expression in the submandibular gland is differentially regulated by androgens in males and thyroid hormone in females.

    Conclusions:

    • The detailed sequence and structural analysis of the human renin gene provide insights into its processing and activation pathways.
    • Understanding the regulation of renin gene expression in different species and tissues is key to understanding its role in physiological and pathological conditions.