@misc{10481/93044,
year = {2024},
month = {4},
url = {https://hdl.handle.net/10481/93044},
abstract = {Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate
immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand
for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can
act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding,
most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to
characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+
metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter
Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the
Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant
lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had
antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids,
effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and
modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts
modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially
reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.},
organization = {Grant PID2020-112768RB-I00 funded by
MICIU/AEI/10.13039/501100011033},
organization = {Instituto de Salud Carlos III
(ISCIII), PI21/00952, co-funded by the European Union},
organization = {Grants AAGR-468-UGR20 and P20–00695 funded by the Consejería de Universidad,
Investigación e Innovación of Junta de Andalucía and by
“ERDF A way of making Europe”},
organization = {FPU fellowship program of the Ministry of Education},
organization = {Plan propio of the University
of Granada},
organization = {Instituto de Salud Carlos
III, Spain},
organization = {US National
Institutes of Health [grants R01 AI101171 and R01 AI127793]},
publisher = {Elsevier},
keywords = {Intestinal inflammation markers},
keywords = {Calprotectin},
keywords = {Intestinal epithelium},
title = {Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids},
doi = {10.1016/j.biopha.2024.116555},
author = {González, R. and Ceacero Heras, Diego and Tena Garitaonaindia, Mireia and Álvarez Mercado, Ana Isabel and Gámez Belmonte, María de los Reyes and Chazin, Walter and Sánchez De Medina López-Huertas, Fermín and Martínez Augustín, María Olga},
}