Smooth muscle cell Piezo1 depletion results in impaired contractile properties in murine small bowel
Piezo1 is a mechanosensitive cation channel expressed in intestinal muscularis cells (IMCs), including smooth muscle cells (SMCs), interstitial cells of Cajal, and Pdgfrα+ cells, which form the SIP syncytium, crucial for GI contractility. Here, we investigate the effects of SMC-specific Piezo1 deletion on small bowel function. Piezo1 depletion results in weight loss, delayed GI transit, muscularis thinning, and decreased SMCs. Ex vivo analyses demonstrated impaired contractile strength and tone, while in vitro studies using IMC co-cultures show dysrhythmic Ca<sup>2+</sup> flux with decreased frequency. Imaging reveal that Piezo1 localizes intracellularly, thereby likely impacting Ca<sup>2+</sup> signaling mechanisms modulated by Ca<sup>2 +</sup> -handling channels located on the sarcoplasmic reticulum and plasma membrane. Our findings suggest that Piezo1 in small bowel SMCs contributes to contractility by maintaining intracellular Ca<sup>2+</sup> activity and subsequent signaling within the SIP syncytium. These findings provide new insights into the complex role of Piezo1 in small bowel SMCs and its implications for GI motility.
Authors
- R. Sergio Solórzano-Vargas
- Ximin He (ORCID: https://orcid.org/0000-0001-8845-4637)
- Elmíra Tokhtaeva
- Nam Phuong N. Nguyen (ORCID: https://orcid.org/0000-0003-4299-5643)
- Matthias Stelzner (ORCID: https://orcid.org/0000-0002-6988-847X)
- Natasha Kushnir (ORCID: https://orcid.org/0009-0008-9040-3669)
- Geoanna Bautista (ORCID: https://orcid.org/0000-0003-0245-9272)
- Martı́n G. Martı́n (ORCID: https://orcid.org/0000-0002-7192-0504)
- Michael Lewis (ORCID: https://orcid.org/0000-0002-1892-4127)
- James Dunn (ORCID: https://orcid.org/0000-0002-6826-7065)
- Nicolle K. Sweeney
- Ana I. Flores (ORCID: https://orcid.org/0000-0002-5019-0434)
- Michael Matthews (ORCID: https://orcid.org/0000-0001-6958-1235)
- Yingjie Du (ORCID: https://orcid.org/0000-0002-8759-2613)
Institutions
- University of California, Los Angeles (US)
- Mattel Children's Hospital (US)
- Broad Center (US)
- VA Greater Los Angeles Healthcare System (US)
- UC Davis Children's Hospital (US)
- University of California, Davis (US)
- Stanford University (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-03-17
- DOI
- https://doi.org/10.1038/s42003-025-07697-6
- Citations
- 5
- Primary Topic
- Erythrocyte Function and Pathophysiology
- Type
- article
- Field-Weighted Citation Impact
- 5.82
Funders
- California Institute for Regenerative Medicine
- American Academy of Pediatrics
- Hartwell Foundation
- Children's Discovery Institute
- University of California, Los Angeles
- University of California, Davis
- California State University, Northridge
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Advancing Translational Sciences