Endothelial-to-mesenchymal transition: Cytokine-mediated pathways that determine endothelial fibrosis under inflammatory conditions.
During the last decade, the endothelial-to-mesenchymal transition (EndMT) process has attracted considerable attention due to associations with the onset of certain diseases, such as organ fibrosis and cancer. Several studies have assessed the mechanisms and signaling pathways that regulate endothelial fibrosis in the context of human pathologies. A number of inflammatory mediators, including pro-inflammatory cytokines, growth factors, oxidative stress, and toxins, induce the conversion of endothelial cells into mesenchymal fibroblast-like cells that promote disease progression. This review is separated into five chapters that critically present current knowledge on EndMT in the context of pathology. First, the main characteristics of EndMT are summarized, with a focus on the endothelial protein pattern changes that modulate the expressions of endothelial/fibrotic markers and extracellular matrix proteins. These expressions could serve as mechanisms for explaining potential EndMT contributions to human pathologies in adults. Second, the main findings supporting a connection between EndMT-mediated endothelial fibrosis and inflammatory conditions are presented. These connections could be linked to the onset and progression of pathological conditions. Third, EndMT inducers are described in detail. This includes considerations on the actions of the first and most well-known EndMT inducer, TGF-β; of the most prominent pro-inflammatory cytokines released during inflammation, such as IL 1-β and TNF-α; and of the NF-κB transcription factor, a common player during inflammation-induced EndMT. Furthermore, thorough attention is given to EndMT induction by endotoxins in the context of bacterial infectious diseases. Additionally, the participation of the inflammatory oxidative stress environment in the EndMT induction was also reviewed. Fourth, the pathophysiological findings of inflammation-induced EndMT are presented, and, fifth, special focus is placed on associations with cancer onset and development. Altogether, this review highlights the important role of EndMT-mediated endothelial fibrosis during inflammation in human pathologies.
Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Ave. Republica 239, 8370134, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile.
Lorena
L
Pérez
Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile.
Natalia
N
Muñoz-Durango
Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Ave. Republica 239, 8370134, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile.
Claudia A
CA
Riedel
Laboratorio de Bionanotecnologia, Universidad Bernardo O Higgins, General Gana 1780, 8370854, Santiago, Chile.
Cesar
C
Echeverría
Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile; Departamento de Reumatología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Ave. Alameda 340, 8331150, Santiago, Chile; Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Ave. Alameda 340, 8331150, Santiago, Chile.
Alexis M
AM
Kalergis
Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Ave. Republica 239, 8370134, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile.
Claudio
C
Cabello-Verrugio
Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas and Facultad de Medicina, Universidad Andres Bello, Ave. Republica 239, 8370134, Santiago, Chile; Millennium Institute on Immunology and Immunotherapy, Ave. Alameda 340, 8331150, Santiago, Chile. Electronic address: fsimon@unab.cl.
Felipe
F
Simon
D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D016207:Cytokines / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000276:immunology* / Q000503:physiopathology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001427:Bacterial Toxins; D016207:Cytokines; D053583:Interleukin-1beta; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha
Endothelium; Fibrosis; Inflammation; Interleukin; TGF-β; TNF-α