Renin-angiotensin system and inflammation update
Autor: | Maria Dolores Sanchez-Niño, Elena Cantero-Navarro, Ana Belen Sanz, Raúl R. Rodrigues-Diez, Adrian M. Ramos, Marta Ruiz-Ortega, Sandra Rayego-Mateos, Beatriz Fernandez-Fernandez, Alberto Ortiz |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Angiotensin receptor T-Lymphocytes 030209 endocrinology & metabolism Inflammation Autoimmunity Blood Pressure Kidney Biochemistry Receptor Angiotensin Type 2 Receptor Angiotensin Type 1 Proinflammatory cytokine Renin-Angiotensin System 03 medical and health sciences 0302 clinical medicine Endocrinology Downregulation and upregulation Renin–angiotensin system medicine Animals Humans Receptor Protein kinase A Molecular Biology Klotho Proteins Chemistry Angiotensin II Water-Electrolyte Balance Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Peptide Fragments Cell biology 030104 developmental biology Gene Expression Regulation Angiotensin-Converting Enzyme 2 medicine.symptom Angiotensin I Signal Transduction |
Zdroj: | Molecular and cellular endocrinology. 529 |
ISSN: | 1872-8057 |
Popis: | The most classical view of the renin-angiotensin system (RAS) emphasizes its role as an endocrine regulator of sodium balance and blood pressure. However, it has long become clear that the RAS has pleiotropic actions that contribute to organ damage, including modulation of inflammation. Angiotensin II (Ang II) activates angiotensin type 1 receptors (AT1R) to promote an inflammatory response and organ damage. This represents the pathophysiological basis for the successful use of RAS blockers to prevent and treat kidney and heart disease. However, other RAS components could have a built-in capacity to brake proinflammatory responses. Angiotensin type 2 receptor (AT2R) activation can oppose AT1R actions, such as vasodilatation, but its involvement in modulation of inflammation has not been conclusively proven. Angiotensin-converting enzyme 2 (ACE2) can process Ang II to generate angiotensin-(1-7) (Ang-(1-7)), that activates the Mas receptor to exert predominantly anti-inflammatory responses depending on the context. We now review recent advances in the understanding of the interaction of the RAS with inflammation. Specific topics in which novel information became available recently include intracellular angiotensin receptors; AT1R posttranslational modifications by tissue transglutaminase (TG2) and anti-AT1R autoimmunity; RAS modulation of lymphoid vessels and T lymphocyte responses, especially of Th17 and Treg responses; interactions with toll-like receptors (TLRs), programmed necrosis, and regulation of epigenetic modulators (e.g. microRNAs and bromodomain and extraterminal domain (BET) proteins). We additionally discuss an often overlooked effect of the RAS on inflammation which is the downregulation of anti-inflammatory factors such as klotho, peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), transient receptor potential ankyrin 1 (TRPA1), SNF-related serine/threonine-protein kinase (SNRK), serine/threonine-protein phosphatase 6 catalytic subunit (Ppp6C) and n-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP). Both transcription factors, such as nuclear factor κB (NF-κB), and epigenetic regulators, such as miRNAs are involved in downmodulation of anti-inflammatory responses. A detailed analysis of pathways and targets for downmodulation of anti-inflammatory responses constitutes a novel frontier in RAS research. |
Databáze: | OpenAIRE |
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