Corticosterone activity during early weaning reprograms molecular markers in rat gastric secretory cells

Abstract

Gastric epithelial cells differentiate throughout the third postnatal week in rats, and become completely functional by weaning time. When suckling is interrupted by early weaning (EW), cell proliferation and differentiation change in the gastric mucosa, and regulatory mechanisms might involve corticosterone activity. Here we used EW and RU486 (glucocorticoid receptor antagonist) to investigate the roles of corticosterone on differentiation of mucous neck (MNC) and zymogenic cells (ZC) in rats, and to evaluate whether effects persisted in young adults. MNC give rise to ZC, and mucin 6, Mist1, pepsinogen a5 and pepsinogen C are produced to characterize these cells. We found that in pups, EW augmented the expression of mucins, Mist1 and pepsinogen C at mRNA and protein levels, and it changed the number of MNC and ZC. Corticosterone regulated pepsinogen C expression, and MNC and ZC distributions. Further, the changes on MNC population and pepsinogen C were maintained until early- adult life. Therefore, by using EW as a model for altered corticosterone activity in rats, we demonstrated that the differentiation of secretory epithelial cells is sensitive to the type of nutrient in the lumen. Moreover, this environmental perception activates corticosterone to change maturation and reprogram cellular functions in adulthood.

Endogenous glucocorticoids prevent gastric metaplasia by suppressing spontaneous inflammation

“…*P ≤ 0.01, **P ≤ 0.001, ***P ≤ 0.0001. curvature 2 months after adrenalectomy (Supplemental Figure 3B). Glucocorticoids have been reported to stimulate differentiation of parietal and chief cells in neonatal mice (28,29). Adrenalectomy did not reduce the number of parietal cells within the greater curvature but did elicit a 43% decrease in mature chief cells (Supplemental Figure 3, C and D).…”

Neonatal- maternal separation primes zymogenic cells in the rat gastric mucosa through glucocorticoid receptor activity

“…In ZC, the moesin gene encodes a cytoskeleton linker protein that is segregated to the apical membrane of gastric cells where it helps to maintain cell polarity 41 , and Bhlha15 encodes Mist1 transcriptional factor that is involved in organization of pepsinogen granules for secretion 39 . Previously, we showed that in rats, early weaning accelerates the differentiation of MNC 24 and ZC 35 . Of note, we demonstrated that corticosterone is an important element in the machinery that coordinates cellular morphological maturation, and we suggested that the changes are maintained to adulthood, indicating a reprogram of growth 35 .…”

“…GR was first described by Munck and Brinck- Johnsen 32 and it is a cytosolic receptor that once activated, rapidly enters the nucleus (t 1/2 = 5–10 min) 33 to bind specific sequences in target genes, which are known as glucocorticoid responsive elements (GRE) 31 , 34 . In the gastric mucosa, GR are expressed during postnatal development and are responsive to circulating glucocorticoids 25 , 35 . In mice and rats, the morphological and functional maturation of gastric mucosa occur concomitant with postnatal development and the glands reach a final configuration by the end of the third week 24 , 36 , 37 .…”

“…The whole growth process involves the action and interaction of milk- born molecules, extension of suckling phase, corticosterone activity, genetic program and microbiota. In each epithelial cell, a set of genes prepares the many steps necessary for differentiation, so that in parietal cells, Atp4b encodes the proton pump (H + -K + /ATPase), which transports ions, acidifying the lumen; in mucous neck cells (MNC), Muc6 encodes the mucin secreted to protect the epithelium, and as MNC turn to zymogenic cells (ZC), the transition is characterized by expression of genes that arrange the cell apex and secretory apparatus 35 , 38 – 40 . In ZC, the moesin gene encodes a cytoskeleton linker protein that is segregated to the apical membrane of gastric cells where it helps to maintain cell polarity 41 , and Bhlha15 encodes Mist1 transcriptional factor that is involved in organization of pepsinogen granules for secretion 39 .…”

O desmame precoce aumenta e reprograma a diferenciação de células mucosas do colo em células zimogênicas na mucosa gástrica de ratos.

“…Nosso grupo já demonstrou que o DP altera a atividade da corticosterona na mucosa gástrica, elevando os níveis hormonais nos primeiros dias de dieta sólida (Ghizoni et al, 2014), além de provocar uma perda de massa corpórea em filhotes (Gama e Alvares, 2000;Zulian et al, 2017). Outros estudos demonstraram o aumento de populações de CMC e CZ, e de células endócrinas secretoras de ghrelina em filhotes (Osaki et al, 2010;Bittar et al, 2016); Zulian et al 2017), além de alterações da proliferação celular e a espessura da glândula gástrica (Gama e Alves, 2000;Zonta, 2017). Essas modificações ocorrem por meio mecanismos de regulação que envolvem a via de sinalização por MAPK (Alvares e Gama, 1993;Osaki et al, 2011;Osaki e Gama, 2013) e receptores de glicocorticóides (Ghizoni et al, 2014).…”