| Autor: |
Qingjuan Wu, Quanmei Sun, Qiang Zhang, Ning Wang, Wenliang Lv, Dong Han |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Pharmaceuticals, Vol 17, Iss 5, p 644 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1424-8247 |
| DOI: |
10.3390/ph17050644 |
| Popis: |
The mechanobiological response mechanism of the fenestrae of liver sinusoidal endothelial cells (LSECs) to the physical stiffness of the extracellular matrix (ECM) remains unclear. We investigated how the mechanical properties of their substrates affect the LSECs’ fenestrae by the nitric oxide (NO)-dependent pathway and how they relate to the progression of hepatic sinus capillarization during liver fibrosis. We detected different stiffnesses of ECM in the progress of liver fibrosis (LF) and developed polyacrylamide hydrogel (PAM) substrates to simulate them. Softer stiffness substrates contributed to LSECs maintaining fenestrae phenotype in vitro. The stiffness of liver fibrosis tissue could be reversed in vivo via treatment with anti-ECM deposition drugs. Similarly, the capillarization of LSECs could be reversed by decreasing the ECM stiffness. Our results also indicate that the NO-dependent pathway plays a key regulatory role in the capillarization of ECM-LSECs. Our study reveals ECM-induced mechanotransduction of capillarized LSECs through a NO-dependent pathway via a previously unrevealed mechanotransduction mechanism. The elucidation of this mechanism may offer precise biomechanics-specific intervention strategies targeting liver fibrosis progression. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
