Language
English
Publication Date
8-18-2023
Journal
iScience
DOI
10.1016/j.isci.2023.107283
PMID
37520701
PMCID
PMC10372839
PubMedCentral® Posted Date
7-14-2023
PubMedCentral® Full Text Version
Post-print
Abstract
The cardiac fibroblast interacts with an extracellular matrix (ECM), enabling myofibroblast maturation via a process called mechanosensing. Although in the aging male heart, ECM is stiffer than in the young mouse, myofibroblast development is impaired, as demonstrated in 2-D and 3-D experiments. In old male cardiac fibroblasts, we found a decrease in actin polymerization, α-smooth muscle actin (α-SMA), and Kindlin-2 expressions, the latter an effector of the mechanosensing. When Kindlin-2 levels were manipulated via siRNA interference, young fibroblasts developed an old-like fibroblast phenotype, whereas Kindlin-2 overexpression in old fibroblasts reversed the defective phenotype. Finally, inhibition of overactivated extracellular regulated kinases 1 and 2 (ERK1/2) in the old male fibroblasts rescued actin polymerization and α-SMA expression. Pathological ERK1/2 overactivation was also attenuated by Kindlin-2 overexpression. In contrast, old female cardiac fibroblasts retained an operant mechanosensing pathway. In conclusion, we identified defective components of the Kindlin/ERK/actin/α-SMA mechanosensing axis in aged male fibroblasts.
Keywords
Cardiovascular medicine, Pathophysiology, Molecular microbiology
Published Open-Access
yes
Recommended Citation
Angelini, Aude; Trial, JoAnn; Saltzman, Alexander B; et al., "A Defective Mechanosensing Pathway Affects Fibroblast-to-Myofibroblast Transition in the Old Male Mouse Heart" (2023). Faculty and Staff Publications. 256.
https://digitalcommons.library.tmc.edu/baylor_docs/256
Graphical Abstract
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Cardiology Commons, Cardiovascular Diseases Commons, Medical Molecular Biology Commons, Pathological Conditions, Signs and Symptoms Commons, Pathology Commons