ArticleProceedings of the National Academy of Sciences of the United States of America2012
Forkhead transcription factor FoxA1 regulates sweat secretion through Bestrophin 2 anion channel and Na-K-Cl cotransporter 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45 citing papers in PubMed, 79 citations in OpenAlex.
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- K31 as a novel marker for clear secretory cells in human eccrine sweat glands.Journal of molecular histology · 2020Trial
- A neurocutaneous NaScience advances · 2026Article
- Association Between Genetically Proxied SLC12A2 Inhibition and Inflammatory Bowel Disease: A Mendelian Randomization Study.Biochemical genetics · 2026Article
- Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome.Nature communications · 2025Article
- Characterization of odor markers associated with aging in old ICR mice.Scientific reports · 2025Article
- Prolactin and heat stress; focus on domestic ruminants.Journal of animal science · 2025Review
- Human and rat ex vivo sweat glands for the observation of acetylcholine induced intracellular calcium signalling.PloS one · 2025Article
- Overview of chromatin regulatory processes during surface ectodermal development and homeostasis.Developmental biology · 2024Review
- Article
- Skin-Interfaced Wearable Sweat Sensors for Precision Medicine.Chemical reviews · 2023Review
- Differential antigen expression between human apocrine sweat glands and eccrine sweat glands.European journal of histochemistry : EJH · 2023Article
- [Research advances on the regulatory mechanism of sweat secretion ion channels of eccrine sweat glands].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- [Research advances on signaling pathways affecting sweat gland development and their involvement in the reconstitution of sweat adenoid cells in vitro].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- Foxa1 mediates eccrine sweat gland development through transcriptional regulation of Na-K-ATPase expression.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2022Article
- Structure and Function of the Bestrophin family of calcium-activated chloride channels.Channels (Austin, Tex.) · 2021Review
- Structural and functional characterization of the bestrophin-2 anion channel.Nature structural & molecular biology · 2020Article
- Novel Human NKCC1 Mutations Cause Defects in Goblet Cell Mucus Secretion and Chronic Inflammation.Cellular and molecular gastroenterology and hepatology · 2020Article
- Skewed macrophage polarization in aging skeletal muscle.Aging cell · 2019Article
- Transcriptomics of Tasmanian Devil (Genes · 2019Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Body temperature is maintained in a narrow range in mammals, primarily controlled by sweating. In humans, the dynamic thermoregulatory organ, comprised of 2-4 million sweat glands distributed over the body, can secrete up to 4 L of sweat per day, thereby making it possible to withstand high temperatures and endure prolonged physical stress (e.g., long-distance running). The genetic basis for sweat gland function, however, is largely unknown. We find that the forkhead transcription factor, FoxA1, is required to generate mouse sweating capacity. Despite continued sweat gland morphogenesis, ablation of FoxA1 in mice results in absolute anihidrosis (lack of sweating). This inability to sweat is accompanied by down-regulation of the Na-K-Cl cotransporter 1 (Nkcc1) and the Ca(2+)-activated anion channel Bestrophin 2 (Best2), as well as glycoprotein accumulation in gland lumens and ducts. Furthermore, Best2-deficient mice display comparable anhidrosis and glycoprotein accumulation. These findings link earlier observations that both sodium/potassium/chloride exchange and Ca(2+) are required for sweat production. FoxA1 is inferred to regulate two corresponding features of sweat secretion. One feature, via Best2, catalyzes a bicarbonate gradient that could help to drive calcium-associated ionic transport; the other, requiring Nkcc1, facilitates monovalent ion exchange into sweat. These mechanistic components can be pharmaceutical targets to defend against hyperthermia and alleviate defective thermoregulation in the elderly, and may provide a model relevant to more complex secretory processes.
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