June 21, 2017

Field: Life science and medicine; Keywords: sweat gland, visualization of the Three-dimensional
Structure , heat stroke, hyperhidrosis, antiperspirant

Successful Visualization of the Three-dimensional
Structure of the Sweat Gland, which Regulates
Body Temperature-Hope for the Explanation and Treatment of Heatstroke andHyperhidrosis and the Development of Next-generation
Antiperspirants[Research Results at a Glance] Successful visualization of the complicated 3D structure of the sweat gland and detailed
explanation of the contraction of the gland during sweating.
 Comprehending the mechanism of sweat gland contraction requires the understandingof the structure of complex sweat glands; however, the existing method(two-dimensional structural analysis) cannot provide sufficient information tounderstand the mechanism of contraction.
 This information might lead to the clarification of the mechanism of sweat glandcontraction during sweating, which will be immensely useful for the elucidation andtreatment of heatstroke and hyperhidrosis, as well as the development of
next-generation antiperspirants.
OutlineOur Osaka University researchgroup, including Guest Professor
Fumihiro Okada, Laboratory ofAdvanced
CosmeticSciences,
Graduate School of PharmaceuticalSciences, Osaka University, Professor
Kiyotoshi Sekiguchi of the Research
Department of the Protein ResearchInstitute,andProfessor
IchiroKatayamaofthe Dermatology
Department of Integrated Medicine at
the Graduate School of Medicine,
succeeded, for the first time, atvisualizing the 3D structure of aFigure 1: Detailed 3D structure of a sweat gland
revealed in this studyhuman sweat gland, which is expected to allow the understanding of the contraction of thesweat glands during sweating (Figure 1).
Clarifying the mechanism by which the sweat gland contracts during perspiration requires
the understanding of its structure in detail. However, because the sweat glands have acomplicated three-dimensional structure, elucidating their structure by using
conventional two-dimensional structural analysis was not possible.
Background of the research
Because of global warming and the emergence of a super-aged society, increases in thenumbers of patients with hyperhidrosis and heatstroke have become a social problem.
Improving the impaired sweating function noted in these disorders requires theunderstanding of the structure of the sweat gland and the manner in which it contracts
during perspiration. The sweat gland is a single tubular exocrine gland composed of asecretoy duct and a excretoty duct, and the sweat released at the secretoy duct isdischarged to the skin surface through the excretoty duct. The secretoy duct at the end of
the sweat gland and a portion of the excretoty duct are intricately folded into a coil shape,
similar to a tangled ball of string. The outermost layer of the secretoy duct of this sweat
gland, present in this coil region, is surrounded by the myoepithelium, which is said tocontract during sweating. However, because the sweat gland has such a complicatedstructure, its intricacies could not be clarified using conventional analysis.
Research Content
Our research group has succeededin visualizing the 3D structure of ahuman sweat gland by using
whole-mount immunostaining. In
order to understand the complex
coiled structure of the sweat gland,
we first selected markers that can beused to identify each part of thehuman sweat gland. By using thesemarkerstovisualize
thethree-dimensional structure of thesweat gland, we found that the tubesof the secretory gland within thecoiled structure had adopted aFigure 2: The 3D Arrangement of Myoepithelial
twisted 3D orientation, almost like aCells and Nerve Fibers in the Secretory
wrung-out towel. The myoepithelial
Part of a Human Sweat Glandcells covering this secretoy duct
were arranged in the direction in which they had been wrung. In addition, by visualizing thenerves necessary to conduct the stimulus that cause perspiration, we found that theysurrounded only the myoepithelial cells of the secretoy duct (Figure 2). This characteristic
3D structure is completely different from that of other secretory glands (such as themammary gland and salivary gland); therefore, we concluded that the sweat gland secretes
sweat via a unique secretion mechanism.
Social impact of these research results (significance of these research results)
We have revealed the detailed 3D structure of a human sweat gland, which is important incontraction during sweating. Understanding the contraction of the sweat gland isindispensable for the treatment of impaired perspiration patterns. If our findings lead tofurther explanation of the basic mechanism of sweat gland contraction during sweating,further understanding and even treatment of disorders resulting from impaired sweating
function (heatstroke and hyperhidrosis) might become possible. Further, in the realm ofantiperspirants, which have, to date, functioned only as “lids” for the openings of sweat
glands, direct action of the sweat glands might realize antiperspirants with novel capability
to directly control the amount of perspiration.
Remarks
These findings will be published in the American science journal PLOS ONE (Online) on
June 22, 2017 at 4 AM Japan time.
Title: “Three-dimensional Cell Shapes and Arrangements in Human Sweat Glands asRevealed by Whole-mount Immunostaining”
Author names: Ryuichiro Kurata1, 2, 3*, Sugiko Futaki3, Itsuko Nakano3, Fumitaka Fujita1, 2,Atsushi Tanemura4, Hiroyuki Murota4, Ichiro Katayama4, Fumihiro Okada1, 2,and Kiyotoshi Sekiguchi3,***First author**Corresponding author
1) Osaka University, Graduate School of Pharmaceutical Sciences, Laboratory for Advanced
Cosmetic Science (Mandom)
2) Mandom Corporation, Foundational Research Laboratory
3) Osaka University, Protein Research Institute, Research Department
4) Osaka University, Graduate School of Medicine, Dermatology Department of Integrated Medicine

This study was performed with funding from the Japan Society for the Promotion ofScience Grant-in-Aid for Scientific Research 16K19721 (The Three-dimensional StructuralAnalysis of the Contractile Coil Element of the Human Sweat Gland, Responsible for
Thermoregulation, and Adjacent Blood Vessels and Nerves )Glossaries*1 Laboratory of Advanced Cosmetic Science, Graduate School of PharmaceuticalSciences, Osaka University
Jointly set up in June 2015 by Graduate School of Pharmaceutical Sciences, OsakaUniversity, and Mandom Corporation. This laboratory accepts financial support fromprivate enterprises and aims to produce excellent research results on common themes injoint research conducted on equal footing. This laboratory is an independent researchorganization set up within Osaka University and conducts flexible and speedy research
activities through discussions between Osaka University and Mandom.

*2 Coiled Structure of a sweat glandA sweat gland is a single tubular exocrine gland, and the end part of a sweat gland isfolded intricately in coiled structure like thread waste entanglement. The outmost layerof the secretory duct in this coiled area is surrounded by myoepithelial cells and contracts
in sweating.
*3 Whole-mount immunostaining
A method that involves the staining of an entire tissue or organ for the investigation of thespatial distribution of cells therein.

Inquiries<About the research contents>
・Guest Professor Fumihiro Okada
Laboratory of Advanced Cosmetic Science, Graduate School of PharmaceuticalSciences, Osaka University
TEL：06-6105-5792
FAX: 06-6105-5790
E-mail: okada-f@phs.osaka-u.ac.jp<About this news release>
・General Affairs Division, Graduate School of Pharmaceutical Sciences, Osaka University
TEL:06-6879-8144
FAX:06-6879-8154
E-mail: yakugaku-syomu@office.osaka-u.ac.jp
・mandom corp.
Public Relations Div.
mail: press@mandom.com
Please contact us in Japanese or English.

[Comment by the Researchers]
During evolution, and in order to avoid lethal increases in body temperature, human beingscame to possess sweat glands throughout their body and chose to accomplish
thermoregulation via sweating. This function is absent in other animals. The sweating
function of our evolutionarily immature sweat gland tends to change according to our living
environment and can become a social problem (such as heatstroke due to global warmingor a decrease in the quality of life due to conditions such as hyperhidrosis). However, thecurrent model of perspiratory function, necessary for the understanding and treatment of theunderlying causes of impaired perspiration, is quite sparsely detailed compared with that ofother organs. Studies on this shortcoming of our understanding of the sweating function
characteristic of human skin tissue can, by forming a strong basis on which further studies
can be performed, lead to applicable findings in the future. Thus, we have been developing
techniques to isolate individual sweat gland cells, identifying sweat gland stem cells, andanalyzing the 3D structure of sweat glands (this press release). In order to overcome
disorders of impaired perspiratory function, we pledge to continue our research efforts.