title: Transforming growth factor-beta and Forkhead box O transcription factors as cardiac fibroblast regulators.
abstract: Fibroblasts play several homeostatic roles, including electrical coupling, paracrine signaling and tissue repair after injury. Fibroblasts have low secretory activity. However, in response to injury, they differentiate to myofibroblasts. These cells have an increased extracellular matrix synthesis and secretion, including collagen fibers, providing stiffness to the tissue. In pathological conditions myofibroblasts became resistant to apoptosis, remaining in the tissue, causing excessive extracellular matrix secretion and deposition, which contributes to the progressive tissue remodeling. Therefore, increased myofibroblast content within damaged tissue is a characteristic hallmark of heart, lung, kidney and liver fibrosis. Recently, it was described that cardiac fibroblast to myofibroblast differentiation is triggered by the transforming growth factor β1 (TGF-β1) through a Smad-independent activation of Forkhead box O (FoxO). FoxO proteins are a transcription factor family that includes FoxO1, FoxO3, FoxO4 and FoxO6. In several cells types, they play an important role in cell cycle arrest, oxidative stress resistance, cell survival, energy metabolism, and cell death. Here, we review the role of FoxO family members on the regulation of cardiac fibroblast proliferation and differentiation.
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Norambuena-Soto
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: Constanza
authors.initials: C
authors.lastname: Núñez-Soto
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Sanhueza-Olivares
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: Nicole
authors.initials: N
authors.lastname: Cancino-Arenas
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: David
authors.initials: D
authors.lastname: Mondaca-Ruff
authors.affiliation: Facultad de Medicina; Universidad de Chile.
authors.forename: Raul
authors.initials: R
authors.lastname: Vivar
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Díaz-Araya
authors.affiliation: Facultad de Química, Pontificia Universidad Católica de Chile.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Mellado
authors.affiliation: Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile.|Centro de Estudios Moleculares de la Célula, Universidad de Chile.
authors.forename: Mario
authors.initials: M
authors.lastname: Chiong
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D058628:Myofibroblasts / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta
keywords: FoxO; TGF-β; fibroblast; fibrosis; myofibroblast; transcription factor