# Long-Term Hypoxia Upregulates Wnt and TGFβ1 Signaling in Eccrine Sweat Gland Cells In Vitro

## TL;DR

This study shows that low oxygen conditions boost key cell signaling pathways in sweat gland cells, which could help in developing treatments for damaged sweat glands.

## Contribution

The study reveals that long-term hypoxia upregulates Wnt and TGFβ1 signaling in cultured eccrine sweat gland cells.

## Key findings

- Culturing sweat gland cells in 0.5% O2 increases HIF-1, Wnt/β-Catenin, and TGFβ1 signaling.
- Low oxygen conditions enhance the expression of undifferentiated cell markers in sweat gland cells.
- The findings suggest hypoxia supports stemness in sweat gland cells, aiding regeneration research.

## Abstract

Eccrine sweat glands play a vital role in human thermoregulation; however, their self-repair function is minimal. Therefore, developing methods to regenerate and improve sweat gland function that use cultured sweat gland cells presents an urgent issue. The tissue microenvironment, especially hypoxic niches, essentially maintain cell stemness, highlighting the importance of oxygen concentration in the culture environment. Therefore, we evaluated the effects of different oxygen environments on human sweat glands and their regulatory mechanisms. Human eccrine sweat glands express HIF-1α and HIF-2α, suggesting that they respond to hypoxia in vivo. Primary human-derived eccrine sweat gland cells were cultured for two weeks using the spheroid culture method at 0.5%, 2%, 10%, and 21% O2 concentration. HIF-1, Wnt/β-Catenin, and TGFβ1 signaling increased in sweat gland cells cultured in 0.5% O2 conditions, along with increased undifferentiated cell marker expression. The results of this study will contribute to in vitro research models of sweat glands and treatment development for damage to sweat glands, including burns.