• kidney

    From ScienceDaily@1:317/3 to All on Monday, April 25, 2022 22:30:44
    kidney
    The finding could have implications in the treatment of kidney diseases.


    Date:
    April 25, 2022
    Source:
    Massachusetts General Hospital
    Summary:
    The kidney carries out important functions via microscopic
    functional units called nephrons. Researchers are investigating
    which factors control the formation and function of specific
    segments of the nephron, called the distal nephron. Their findings
    could have implications in the treatment of kidney diseases.



    FULL STORY ========================================================================== Proper function of the kidney is critical for concentrating urine,
    regulating blood pressure, and for the tight control of electrolyte
    levels in the blood.

    The kidney achieves these important functions through many microscopic functional units, called nephrons. These nephrons consist of different
    segments with distinct functions. How these segments form during
    development and how their function is maintained in the adult is only
    partially understood.


    ==========================================================================
    A team of MGH investigators has now investigated which factors control
    the formation and function of specific segments of the nephron, called
    the distal nephron.

    The distal nephron is particularly important for the ability of the
    kidney to concentrate urine, regulate blood pressure, and control
    calcium and magnesium blood levels. Parts of the distal nephron have
    specific salt transporters, which are the main targets of medicine's most effective diuretics, used in the treatment of hypertension and chronic
    kidney disease. Thus, understanding how their function is regulated has important implications for these common diseases.

    Alexander G. Marneros, MD, PhD, a physician-scientist at Mass
    General's Cutaneous Biology Research Center and an associate professor
    of Dermatology at Harvard Medical School, and colleagues set out to
    identify key regulators of distal nephron function. In a new research
    article published in the journal Nature Communications, he and his team
    show that two very similar proteins, the transcription factors AP-2a
    and AP-2b, regulate the function of two distinct segments of the distal
    nephron in mice.

    Previously, Marneros showed in work published in Developmental Cell
    in 2020 that AP-2b is required for the formation of the segment of
    the distal nephron that is targeted by thiazide diuretics: the distal convoluted tubule. This prompted him to ask whether the closely related
    protein AP-2a also has a function in the kidney. His team found that while AP-2b function in the kidney is required for survival by regulating the development and function of distal convoluted tubules, AP-2a is important
    for the proper function of a different segment of the distal nephron,
    called the collecting duct, which is involved in the kidney's ability to concentrate urine. Notably, loss of even only half of AP-2b levels causes progressive kidney disease, whereas complete loss of AP-2a resulted in
    less severe kidney abnormalities.

    "These findings show that AP-2a and AP-2b are important regulators
    of distinct segments of the distal nephron. These new observations in
    genetic mouse models are important contributions to our understanding of
    how specific segments of the kidney are regulated on a molecular level,"
    says Marneros.

    "A detailed understanding of the mechanisms that not only lead to the
    formation of distal nephron segments but also that maintain the proper
    function of these segments in the adult is important for future novel therapeutic approaches in the management of various kidney diseases,"
    he adds.

    This study was supported by the National Institutes of Health and
    institutional funding from Massachusetts General Hospital.


    ========================================================================== Story Source: Materials provided by Massachusetts_General_Hospital. Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Joseph O. Lamontagne, Hui Zhang, Alia M. Zeid, Karin Strittmatter,
    Alicia
    D. Rocha, Trevor Williams, Sheryl Zhang, Alexander G. Marneros.

    Transcription factors AP-2a and AP-2b regulate distinct segments of
    the distal nephron in the mammalian kidney. Nature Communications,
    2022; 13 (1) DOI: 10.1038/s41467-022-29644-3 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/04/220425085719.htm

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