Immediate and Late Effects of Early Weaning on Rat Gastric Cell Differentiation

Silva, Melissa Teles; Silva, Kethleen Mesquita da; Rattes, Isadora Campos; Zonta, Gizela Maria Agostini; Costa, Aline Vasques da; Costa, Raquel; Nogueira, Ludimila; Ogias, Daniela; Gama, Patrı́cia

doi:10.3390/ijms21010196

Cited by 6 publications

(16 citation statements)

References 63 publications

(125 reference statements)

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“…Additionally, when niches were closely observed, a resilient proliferative activity remained higher at the base after EW, compared with the S group at 60 days. Such an area is a secondary compartment for epithelial proliferation (Han et al, 2019 ; Burclaff et al, 2020 ), and the residing zymogenic cell population is increased by EW (Teles Silva et al, 2020 ). Due to these combined data, we investigated some of the parameters that could be involved in cell trans-differentiation.…”

Section: Resultsmentioning

confidence: 99%

“…Two times a day, EW rats received food and water through disposable Pasteur pipettes and were massaged to facilitate excretion, mimicking maternal care. The number of pups with the dam was controlled to avoid obesity, and the experiments proceeded when the body mass was observed to change according to the patterns previously established (Teles Silva et al, 2020 ).…”

Section: Methodsmentioning

confidence: 99%

“…Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used, and methods were followed as described before (Teles Silva et al, 2020 ) for scraped samples from gastric mucosa. Briefly, after RNA isolation (TRIzol combined with PureLink ® RNA Mini Kit, Invitrogen) and quantification (NanoDrop, Thermo Fisher Scientific), 3 μg of RNA were used for cDNA synthesis with the Superscript III Reverse Transcriptase enzyme (200 U/μl, Invitrogen).…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, when the proliferative stimulus is evaluated as a trigger for cell differentiation, mucous neck cells, and zymogenic populations are increased in developing young-adult rats, and, for these developmental stages, such regulation is dependent on corticosterone activity (Osaki et al, 2010 ; Zulian et al, 2017 ). Importantly, in the adult gastric mucosa, the distribution of zymogenic cells remains high in early weaned rats (Teles Silva et al, 2020 ). When the recent studies are combined, they do not show irregular growth, erosion, and restitution failure after EW, as it had been demonstrated before (Ackerman et al, 1975 , 1978 ; Glavin and Pare, 1985 ), but they do not evaluate whether there would be long-lasting effects to predispose the stomach for inflammation or lesions.…”

Section: Introductionmentioning

confidence: 99%

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Lifelong Adaptation of Gastric Cell Proliferation and Mucosa Structure to Early Weaning-Induced Effects

et al. 2021

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The gastric mucosa is disturbed when breastfeeding is interrupted, and such early weaning (EW) condition permanently affects the differentiation of zymogenic cells. The aim of the study was to evaluate the immediate and long-term effects of EW on gastric cell proliferation, considering the molecular markers for cell cycle, inflammation, and metaplasia. Overall, we investigated the lifelong adaptation of gastric growth. Wistar rats were divided into suckling-control (S) and EW groups, and gastric samples were collected at 18, 30, and 60 days for morphology, RNA, and protein isolation. Inflammation and metaplasia were not identified, but we observed that EW promptly increased Ki-67-proliferative index (PI) and mucosa thickness (18 days). From 18 to 30 days, PI increased in S rats, whereas it was stable in EW animals, and such developmental change in S made its PI higher than in EW. At 60 days, the PI decreased in S, making the indices similar between groups. Spatially, during development, proliferative cells spread along the gland, whereas, in adults, they concentrate at the isthmus-neck area. EW pushed dividing cells to this compartment (18 days), increased PI at the gland base (60 days), but it did not interfere in expression of cell cycle molecules. At 18 days, EW reduced Tgfβ2, Tgfβ3, and Tgfbr2 and TβRII and p27 levels, which might regulate the proliferative increase at this age. We demonstrated that gastric cell proliferation is immediately upregulated by EW, corroborating previous results, but for the first time, we showed that such increased PI is stable during growth and aging. We suggest that suckling and early weaning might use TGFβs and p27 to trigger different proliferative profiles during life course.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lifelong Adaptation of Gastric Cell Proliferation and Mucosa Structure to Early Weaning-Induced Effects

et al. 2021

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“…EW and the change to solid food affect the development of pulmonary and GI tracts and interfere in cell proliferation and differentiation. In the gastric mucosa, EW stimulates cell proliferation through MAPK signaling (Cummins & Thompson, 2002; Osaki et al, 2011) and it interferes in cell differentiation (Zulian et al, 2017; Teles Silva et al, 2019). Similarly, we demonstrated that EW also reduces the differentiation of intestinal goblet cells in rats (da Costa et al, 2019).…”

Section: Breastmilk Composition and Its Antimicrobial Rolementioning

confidence: 99%

Breastfeeding importance and its therapeutic potential against SARS‐CoV‐2

2021

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During postnatal development, colostrum and breastmilk are sequentially the first sources of nutrition with protein components and bioactive molecules that confer protection and immunostimulatory function to the gut. Caseins, whey proteins, secretory immunoglobulin A (sIgA), mucins, tryptophan, and growth factors are among milk‐borne elements that are directly important in the control of mucosa development and protection. Consequently, breastfeeding is associated with the low incidence of gastrointestinal inflammation and with the decrease in respiratory diseases during postnatal period. The novel coronavirus (SARS‐CoV‐2) binds to angiotensin II‐converting enzyme (ACE2) on the cell membrane, allowing virus entrance, replication, and host commitment. ACE2 is expressed by different cell types, which include ciliated cells in the lungs and enterocytes in the intestine. Such cells are highly active in metabolism, as they internalize molecules to be processed and used by the organism. The disruption of ACE2 impairs leads to intestinal inflammation and decreased synthesis of serotonin, affecting motility. By reviewing the effects of SARS‐CoV‐2 in the gastrointestinal and respiratory tracts in infants, and gut responses to breastfeeding interruption, we suggest that it is important to maintain breastfeeding during SARS‐CoV‐2 infection, as it might be essential to protect newborns from gastrointestinal‐associated disorders and relieve disease symptoms.

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Breastfeeding lifespan control of growth, maintenance, and metabolism of small intestinal epithelium

Costa

Rattes

Goes

et al. 2023

Journal Cellular Physiology

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Gastrointestinal epithelial cells respond to milk‐born molecules throughout breastfeeding, influencing growth, and development. The rapid renewal of the small intestine depends on the proliferation in the crypt that drives cell fates. We used early weaning model to investigate immediate and late effects of breastfeeding on proliferation, differentiation of jejunal epithelial cells. Wistar rats were either allowed to suckle (S) until 21 postnatal days or submitted to early weaning (EW) at 15 days. By comparing ages (18, 60, and 120 days), we found that EW decreased Ki67 indices and villi height at 18 and 60 days (p < 0.05), and at 120 days they were similar between diets. Proliferative reduction and augmented expression of Cdkn1b (p27 gene) were parallel. In the stem cell niche, EW increased the number and activity (Defa24) of Paneth cells at 18 and 60 days (p < 0.05), and Lgr5 and Ascl2 genes showed inverted responses between ages. Among target cells, EW decreased goblet cell number at 18 and 60 days (p < 0.05) and increased it at 120 days (p < 0.05), whereas enteroendocrine marker genes were differentially altered. EW reduced enterocytes density at 18 days (p < 0.05), and at 120 days this population was decreased (vs. 60 days). Among cell fate crypt‐controlling genes, Notch and Atoh1 were the main targets of EW. Metabolically, intraperitoneal glucose tolerance was immediately reduced (18 days), being reverted until 120 days (p < 0.05). Currently, we showed that breastfeeding has a lifespan influence on intestinal mucosa and on its stem cell compartment. We suggest that, although jejunum absorptive function is granted after early weaning, the long lasting changes in gene expression might prime the mucosa with a different sensitivity to gut disorders that still have to be further explored.

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Immediate and Late Effects of Early Weaning on Rat Gastric Cell Differentiation

Cited by 6 publications

References 63 publications

Lifelong Adaptation of Gastric Cell Proliferation and Mucosa Structure to Early Weaning-Induced Effects

Lifelong Adaptation of Gastric Cell Proliferation and Mucosa Structure to Early Weaning-Induced Effects

Breastfeeding importance and its therapeutic potential against SARS‐CoV‐2

Breastfeeding lifespan control of growth, maintenance, and metabolism of small intestinal epithelium

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