Fam3D (FAM3D in human) is a homeostatic protein expressed mainly in gastrointestinal tract that plays an essential role in promoting colon mucosal development and homeostasis. However, the mechanistic basis for the action of Fam3D, particularly its relationship to colon mucosal development and microbiome balance, is less clear. In this study, Fam3D expression was increased in colon epithelial cells of germ-free (GF) Fam3D+/+ mice following E. coli infection and GF Fam3D-/- mice were more susceptible to E. coli colonization in the colon. In chemically induced colitis and colon cancer, GF Fam3D-/- mice showed more severe inflammatory responses, colon mucosal damage, and tumorigenesis. Unlike SPF mice, GF Fam3D-/- mice exhibited decreased production of the gut barrier protein Muc2. Mechanism study revealed that in colon epithelial cells, LPS upregulated Fam3D expression through TLR4, while Fam3D promoted Muc2 production through Fpr1 and Fpr2. In addition, Fam3D also upregulated the expression of MAP kinase phosphatase 1 (MKP-1) which is crucial for restraining inflammatory responses. Fam3D deficiency reduced MKP-1 expression, thereby increasing IL-1β and TNF-α production in colon mucosa of GF mice. Thus, Fam3D is critical in colon homeostasis and constitutes a therapeutic target for inflammatory colon diseases.
| Published in | International Journal of Gastroenterology (Volume 7, Issue 1) |
| DOI | 10.11648/j.ijg.20230701.11 |
| Page(s) | 1-14 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Fam3D, Muc2, MKP-1, Infection, Inflammation, Colon Cancer
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APA Style
Keqiang Chen, Weiwei Liang, Teizo Yoshimura, Wanghua Gong, Jiaqiang Huang, et al. (2023). The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis. International Journal of Gastroenterology, 7(1), 1-14. https://doi.org/10.11648/j.ijg.20230701.11
ACS Style
Keqiang Chen; Weiwei Liang; Teizo Yoshimura; Wanghua Gong; Jiaqiang Huang, et al. The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis. Int. J. Gastroenterol. 2023, 7(1), 1-14. doi: 10.11648/j.ijg.20230701.11
AMA Style
Keqiang Chen, Weiwei Liang, Teizo Yoshimura, Wanghua Gong, Jiaqiang Huang, et al. The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis. Int J Gastroenterol. 2023;7(1):1-14. doi: 10.11648/j.ijg.20230701.11
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Download@article{10.11648/j.ijg.20230701.11,
author = {Keqiang Chen and Weiwei Liang and Teizo Yoshimura and Wanghua Gong and Jiaqiang Huang and Simone Difilippantonio and Georgette Jones and Jimmy York and Giorgio Trinchieri and Ying Wang and Ji Ming Wang},
title = {The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis},
journal = {International Journal of Gastroenterology},
volume = {7},
number = {1},
pages = {1-14},
doi = {10.11648/j.ijg.20230701.11},
url = {https://doi.org/10.11648/j.ijg.20230701.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijg.20230701.11},
abstract = {Fam3D (FAM3D in human) is a homeostatic protein expressed mainly in gastrointestinal tract that plays an essential role in promoting colon mucosal development and homeostasis. However, the mechanistic basis for the action of Fam3D, particularly its relationship to colon mucosal development and microbiome balance, is less clear. In this study, Fam3D expression was increased in colon epithelial cells of germ-free (GF) Fam3D+/+ mice following E. coli infection and GF Fam3D-/- mice were more susceptible to E. coli colonization in the colon. In chemically induced colitis and colon cancer, GF Fam3D-/- mice showed more severe inflammatory responses, colon mucosal damage, and tumorigenesis. Unlike SPF mice, GF Fam3D-/- mice exhibited decreased production of the gut barrier protein Muc2. Mechanism study revealed that in colon epithelial cells, LPS upregulated Fam3D expression through TLR4, while Fam3D promoted Muc2 production through Fpr1 and Fpr2. In addition, Fam3D also upregulated the expression of MAP kinase phosphatase 1 (MKP-1) which is crucial for restraining inflammatory responses. Fam3D deficiency reduced MKP-1 expression, thereby increasing IL-1β and TNF-α production in colon mucosa of GF mice. Thus, Fam3D is critical in colon homeostasis and constitutes a therapeutic target for inflammatory colon diseases.},
year = {2023}
}
TY - JOUR T1 - The Homeostatic Protein Fam3D Orchestrates Colon Mucosal Protection Against Infection, Inflammation, and Carcinogenesis AU - Keqiang Chen AU - Weiwei Liang AU - Teizo Yoshimura AU - Wanghua Gong AU - Jiaqiang Huang AU - Simone Difilippantonio AU - Georgette Jones AU - Jimmy York AU - Giorgio Trinchieri AU - Ying Wang AU - Ji Ming Wang Y1 - 2023/02/21 PY - 2023 N1 - https://doi.org/10.11648/j.ijg.20230701.11 DO - 10.11648/j.ijg.20230701.11 T2 - International Journal of Gastroenterology JF - International Journal of Gastroenterology JO - International Journal of Gastroenterology SP - 1 EP - 14 PB - Science Publishing Group SN - 2640-169X UR - https://doi.org/10.11648/j.ijg.20230701.11 AB - Fam3D (FAM3D in human) is a homeostatic protein expressed mainly in gastrointestinal tract that plays an essential role in promoting colon mucosal development and homeostasis. However, the mechanistic basis for the action of Fam3D, particularly its relationship to colon mucosal development and microbiome balance, is less clear. In this study, Fam3D expression was increased in colon epithelial cells of germ-free (GF) Fam3D+/+ mice following E. coli infection and GF Fam3D-/- mice were more susceptible to E. coli colonization in the colon. In chemically induced colitis and colon cancer, GF Fam3D-/- mice showed more severe inflammatory responses, colon mucosal damage, and tumorigenesis. Unlike SPF mice, GF Fam3D-/- mice exhibited decreased production of the gut barrier protein Muc2. Mechanism study revealed that in colon epithelial cells, LPS upregulated Fam3D expression through TLR4, while Fam3D promoted Muc2 production through Fpr1 and Fpr2. In addition, Fam3D also upregulated the expression of MAP kinase phosphatase 1 (MKP-1) which is crucial for restraining inflammatory responses. Fam3D deficiency reduced MKP-1 expression, thereby increasing IL-1β and TNF-α production in colon mucosa of GF mice. Thus, Fam3D is critical in colon homeostasis and constitutes a therapeutic target for inflammatory colon diseases. VL - 7 IS - 1 ER -
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