BET Proteins: An Approach to Future Therapies in Transplantation.
In order to develop new efficient therapies for organ transplantation, it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation, and fibrosis, which lead to rejection and long-term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4, and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes. These proteins recognize acetylated lysines in histones and master transcription factors to recruit regulatory complex and, finally, modify the transcriptional program. Recent studies indicate that BET proteins are essential in the NF-kB-mediated inflammatory response, during the activation and differentiation of Th17-immune cells, and in profibrotic processes. Here, we review this new body of data and highlight the efficiency of BET inhibitors in several models of diseases. The promising results obtained from these preclinical models indicate that it may be time to translate these outcomes to the transplantation field, where epigenetics will be of increasing value in the coming years.
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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Suarez-Alvarez
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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RM
Rodriguez
Cellular Biology of Renal Disease Laboratory, Nephrology Department, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain.
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M
Ruiz-Ortega
Department of Immunology, Hospital Universitario Central de Asturias, Oviedo, Spain.
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C
Lopez-Larrea
D000818:Animals; D002843:Chromatin / Q000235:genetics; D044127:Epigenesis, Genetic; D006084:Graft Rejection / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D005810:Multigene Family; D016377:Organ Transplantation / Q000009:adverse effects*; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002843:Chromatin; D014157:Transcription Factors
basic (laboratory) research/science; immunosuppression/immune modulation; molecular biology; tolerance: mechanisms; translational research/science