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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