Abstract/Details

The Role of Piezo1 Ion Channel-Mediated Mechanotransduction in Regulating Collagen Synthesis during Fibrosis: An In Vitro Study

Rashidi, Neda.   Washington University in St. Louis ProQuest Dissertations & Theses,  2024. 31295139.

Abstract (summary)

Fibrosis, a pathological condition affecting various organs and contributing significantly to mortality, accounts for up to 45% of deaths in industrialized nations. Understanding the mechanobiological signaling pathways in tissues offers a promising avenue for gaining fresh insights into strategies for controlling or reversing fibrosis-related tissue remodeling. Recent research and clinical studies have focused on the use of Adipose-Derived Stem Cells (ASCs) to treat various forms of tissue fibrosis as well as their role in pathologic conditions. This study aimed to enhance our understanding of how ASCs behave in fibrotic environments, particularly in terms of their response to mechanical cues through the Piezo1 ion channel mechanotransduction pathway. Our findings indicate that Piezo1 may play an important role in fibrosis, and modulating Piezo1 activity can influence collagen regulation in ASCs, both in two-dimensional and three-dimensional in vitro models. Moreover, this effect is influenced by the mechanical properties of the substrate. Mechanistically, we observed that Piezo1 modulation can impact the activity and localization of YAP, a key transcriptional regulator. Notably, the depletion of YAP and TAZ did not significantly alter collagen expression patterns in the context of Piezo1 activation, suggesting the existence of potentially independent pathways. These discoveries provide valuable insights into the mechanobiology of human adipose stem cells, particularly in fibrotic microenvironments, highlighting the critical role of Piezo1 in cellular mechanosensing and its implications for tissue engineering and regenerative medicine.

Indexing (details)


Subject
Biomedical engineering;
Bioengineering;
Cellular biology;
Biomechanics
Classification
0541: Biomedical engineering
0202: Bioengineering
0379: Cellular biology
0648: Biomechanics
Identifier / keyword
Collagen; Fibrosis; Mechanobiology; Piezo1 channels; Substrate architecture
Title
The Role of Piezo1 Ion Channel-Mediated Mechanotransduction in Regulating Collagen Synthesis during Fibrosis: An In Vitro Study
Author
Rashidi, Neda
Number of pages
147
Publication year
2024
Degree date
2024
School code
0252
Source
DAI-B 85/11(E), Dissertation Abstracts International
ISBN
9798382593708
Advisor
Guilak, Farshid
Committee member
Lake, Spencer; Pathak, Amit; Wagenseil, Jessica; Tang, Simon
University/institution
Washington University in St. Louis
Department
Mechanical Engineering & Materials
University location
United States -- Missouri
Degree
Ph.D.
Source type
Dissertation or Thesis
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
31295139
ProQuest document ID
3054301791
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
https://www.proquest.com/docview/3054301791