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Genetic deletion of the angiotensin-(1-7) receptor Mas leads to alterations in gut villi length modulating TLR4/PI3K/AKT and produces microbiome dysbiosis.
Metadata
Journalneuropeptides2.411Date
2020 May 18
5 months ago
Type
Journal Article
Volume
2020-Aug / 82 : 102056
Author
Oliveira LP 1, Guimarães VHD 1, Oliveira JR 1, Guimarães ALS 1, de Paula AMB 1, Bader M 2, Santos RASD 3, Santos SHS 4
Affiliation
  • 2. Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany.
  • 3. Institute of Biological Sciences (ICB), Physiology Department, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
  • 4. Institute of Agricultural Sciences (ICA), Food Engineering, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil. Electronic address: [email protected]
Doi
PMIDMESH
Abstract
Renin-Angiotensin System (RAS) is an important peptide cascade involved in physiological processes. RAS homeostasis disruption produces several cardiovascular and metabolic disorders, such as arterial hypertension, atherosclerosis, acute myocardial infarct, obesity, diabetes, metabolic syndrome and increases gastrointestinal tract (GIT) cell proliferation. Angiotensin (Ang)-(1-7) peptide is the main RAS counter-regulatory axis effector. It is formed from ACE2 enzyme and acts mainly through Mas receptor (MasR). In this context, the aim of the present study was to evaluate alterations in small intestine morphology and intestinal microbiota composition in MasR knockout C57BL/6 mice. We analyzed glucose tolerance; insulin sensitivity and blood collected for biochemical parameters as well as small intestine tissues samples for immunohistochemistry. mRNA and bacteria gDNA expression evaluation. mRNA expression was evaluated by qRT-PCR for TLR4, PI3K and AKT. The main results showed that Mas-R-knockout mice presented lower body weight. MasR-knockout mice also presented increased fasted blood glucose and total cholesterol with reduced HDL, lower glucose tolerance and impaired insulin sensitivity. Increased intestinal mucosa length, increased intestinal villi, reduced Lieberkühn crypt depth. The increased expression of cell proliferation markers Ki-67 and Cyclin D1 and increased TLR4, PI3K and AKT expressions were observed with augmented Bacteroidetes and decreased amount of Firmicutes. That results suggests that MasR deletion generated changes in intestinal microbiota, possibly due to a lower neutral amino acids absorption followed by a compensatory increase in intestinal villi length associated with disbiosis and LPS overproduction that ultimately lead to proliferation and cell inflammation.
Keywords: Ang-(1–7) Angiotensin Inflammation Microbiota Small intestine
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Neuropeptidesneuropeptides
Metadata
LocationNetherlands
FromCHURCHILL LIVINGSTONE

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