Gene expression, cell differentiation and gastric functions: can dietary changes during postnatal development disturb the growth program in rats?
Authors: Gama Patricia , Silva Melissa Teles , Silva Kethleen Mesquita , Zonta Gizela M Agostini , Zulian Juliana Guimarães , Ogias Daniela 
Published: November 2023

The development of the gastrointestinal tract depends on proper suckling‐weaning transition. In the gastric mucosa, hormones and milk‐born peptides regulate cell proliferation, differentiation and death. Our hypothesis is that suckling (S) is one of the main regulatory agents during development, and so, changes in dietary pattern or conditions can alter the expression of genes that regulate stem cell niche, cell proliferation and differentiation and consequently the growth, maturation and function. In order to test this idea, we evaluated how early weaning (EW) influences body mass gain, gastric cell proliferation, and the expression of genes that control maturation of mucous surface and neck cells (MNC), and zymogenic (ZC) and parietal cells. Wistar rats were submitted to EW at 15d (Ethical Committee on Animal Use‐ICBUSP 18/2015) and gastric samples were collected at 18, 30 and 60d for RT‐qPCR, immnublotting and imaging. We found that body mass was lower at 18 and 30d in EW group (p<0.01), whereas at 60d, such difference was not detected. EW also increased proliferation index and thickness of mucosa at 18 d (p<0.05), i.e. soon after the onset of treatment. Conversely, an opposite result was observed at 30d, when Ki‐67 immunolabeling was reduced in EW rats (p<0.05). Variations were not detected at 60d. As for genes involved in differentiation, we observed that EW increased mucin 6 (MNC) at 18 and 30d (p<0.05), whereas bhlha15 (Mist1‐terminal differentiation of MNC into ZC) was higher only at 18d (p<0.05). We also detected the increase of msn (Moesin, at 18 and 30d) and gif (Gastric Intrinsic factor) expression at 30 and 60d. Additionally, whereas psga (Pepsinogen A, synthesized during development) decreased at 18 and 30d in EW group (p<0.05), we found an upsurge of Pepsinogen C at 18d (gene and protein), and such response persisted at 30 and 60d (p<0.05). The expression of H+/K+‐ATPase pump (parietal cells) increased after EW at 18 and 60d (p<0.05), but this change was not reflected in the density of cells. As differentiation of secretory cells is determinant for hoemostasis in the gastric gland, and we also evaluated, under fluorescent microscopy, the number of cells that were double‐labeled for acid glycoprotein and Mist1 (transitory population). EW did not alter the size of such compartment, indicating the relevance of such control to the maintenance of epithelial populations. Therefore, we can suggest that EW altered body weight gain and gastric growth in pups and young adults, but such changes did not persist to adulthood. Moreover, we demonstrated that the abrupt interruption of suckling anticipated the expression of genes that regulate the differentiation of cells, and some of these modifications are maintained to adult life, indicating that part of EW responses might be imprinted throughout growth and aging.

Support or Funding Information

PRPG USP (01/2017‐PROAP); São Paulo Research Foundation (FAPESP 2014/21449‐9). Students are recipient of CNPq and CAPES fellowships.