Cx40 Levels Regulate Hypoxia-Induced Changes in the Migration, Proliferation, and Formation of Gap Junction Plaques in an Extravillous Trophoblast Cell Model.

Autor: Rozas-Villanueva FM; Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile., Orellana VP; Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile., Alarcón R; Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile., Maripillan J; Centro Interdisciplinario de Neurociencias de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile., Martinez AD; Centro Interdisciplinario de Neurociencias de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile., Alfaro IE; Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile., Retamal MA; Programa de Comunicación Celular en Cáncer, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago 7550000, Chile.; Center for Membrane Protein Research, Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2024 Jul 06; Vol. 13 (13). Date of Electronic Publication: 2024 Jul 06.
DOI: 10.3390/cells13131150
Abstrakt: Background: Extravillous trophoblasts (EVTs) form stratified columns at the placenta-uterus interface. In the closest part to fetal structures, EVTs have a proliferative phenotype, whereas in the closest part to maternal structures, they present a migratory phenotype. During the placentation process, Connexin 40 (Cx40) participates in both the proliferation and migration of EVTs, which occurs under hypoxia. However, a possible interaction between hypoxia and Cx40 has not yet been established.
Methods: We developed two cellular models, one with "low Cx40" (Jeg-3), which reflected the expression of this protein found in migratory EVTs, and one with "high Cx40" (Jeg-3/hCx40), which reflected the expression of this protein in proliferative cells. We analyzed the migration and proliferation of these cells under normoxic and hypoxic conditions for 24 h. Jeg-3 cells under hypoxia increased their migratory capacity over their proliferative capacity. However, in Jeg-3/hCx40, the opposite effect was induced. On the other hand, hypoxia promoted gap junction (GJ) plaque formation between neighboring Jeg-3 cells. Similarly, the activation of a nitro oxide (NO)/cGMP/PKG-dependent pathway induced an increase in GJ-plaque formation in Jeg-3 cells.
Conclusions: The expression patterns of Cx40 play a crucial role in shaping the responses of EVTs to hypoxia, thereby influencing their migratory or proliferative phenotype. Simultaneously, hypoxia triggers an increase in Cx40 gap junction (GJ) plaque formation through a pathway dependent on NO.
Databáze: MEDLINE
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