Sonmez, U. | bioRxiv Science

bioRxiv2025

PIEZO channels link mechanical forces to uterine contractions in parturition

AbstractMechanical forces are extensively involved in pregnancy and parturition, but their precise roles and mechanisms remain poorly understood. Here, we identify mechanically activated ion channels PIEZO1 and PIEZO2 as key mechanotransducers required for labor progression. Genetic deletion of Piezo1 and Piezo2 in mice resulted in weakened uterine contractions and severe parturition defects. Tissue-specific knockouts revealed that deletion in either the uterus or sensory neurons alone caused modest defects, whereas combined loss significantly impaired labor, demonstrating additive effects. Single-nuclei sequencing showed that loss of PIEZO reduced expression of connexin43 (Gja1), a gap junction protein in uterine smooth muscle cells, suggesting a mechanistic link to impaired contraction. These findings highlight the critical role of PIEZO channels in mechanotransduction during parturition and suggest therapeutic targets for labor dysfunction.

physiology↗

bioRxiv2024

A key role of PIEZO2 mechanosensitive ion channel in adipose sensory innervation

Compared to the well-established functions of sympathetic innervation, the role of sensory afferents in adipose tissues remains less understood. Recent work revealed the anatomical and physiological significance of adipose sensory innervation; however, its molecular underpinning remains unclear. Here, using organ-targeted single-cell RNA sequencing, we identified the mechanoreceptor PIEZO2 as one of the most prevalent receptors in fat-innervating dorsal root ganglia (DRG) neurons. We found that selective PIEZO2 deletion in fat-innervating neurons phenocopied the molecular alternations in adipose tissue caused by DRG ablation. Conversely, a gain-of-function PIEZO2 mutant shifted the adipose phenotypes in the opposite direction. These results indicate that PIEZO2 plays a major role in the sensory regulation of adipose tissues. This discovery opens new avenues for exploring mechanosensation in organs not traditionally considered mechanically active, such as the adipose tissues, and therefore sheds light on the broader significance of mechanosensation in regulating organ function and homeostasis.

neuroscience↗