Estrogen receptors differentially modifies lamellipodial and focal adhesion dynamics in airway smooth muscle cell migration.

Autor: Ambhore NS; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA., Balraj P; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA., Pabelick CM; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA., Prakash YS; Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, USA., Sathish V; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND, USA. Electronic address: s.venkatachalem@ndsu.edu.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 Jan 01; Vol. 579, pp. 112087. Date of Electronic Publication: 2023 Oct 10.
DOI: 10.1016/j.mce.2023.112087
Abstrakt: Sex-steroid signaling, especially estrogen, has a paradoxical impact on regulating airway remodeling. In our previous studies, we demonstrated differential effects of 17β-estradiol (E 2 ) towards estrogen receptors (ERs: α and β) in regulating airway smooth muscle (ASM) cell proliferation and extracellular matrix (ECM) production. However, the role of ERs and their signaling on ASM migration is still unexplored. In this study, we examined how ERα versus ERβ affects the mitogen (Platelet-derived growth factor, PDGF)-induced human ASM cell migration as well as the underlying mechanisms involved. We used Lionheart-FX automated microscopy and transwell assays to measure cell migration and found that activating specific ERs had differential effects on PDGF-induced ASM cell migration. Pharmacological activation of ERβ or shRNA mediated knockdown of ERα and specific activation of ERβ blunted PDGF-induced cell migration. Furthermore, specific ERβ activation showed inhibition of actin polymerization by reducing the F/G-actin ratio. Using Zeiss confocal microscopy coupled with three-dimensional algorithmic ZEN-image analysis showed an ERβ-mediated reduction in PDGF-induced expressions of neural Wiskott-Aldrich syndrome protein (N-WASP) and actin-related proteins-2/3 (Arp2/3) complex, thereby inhibiting actin-branching and lamellipodia. In addition, ERβ activation also reduces the clustering of actin-binding proteins (vinculin and paxillin) at the leading edge of ASM cells. However, cells treated with E 2 or ERα agonists do not show significant changes in actin/lamellipodial dynamics. Overall, these findings unveil the significance of ERβ activation in regulating lamellipodial and focal adhesion dynamics to regulate ASM cell migration and could be a novel target to blunt airway remodeling.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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