Emc3 maintains intestinal homeostasis by preserving secretory lineages | JoVE Visualize

Emc3 maintains intestinal homeostasis by preserving secretory lineages

¹State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.

Mucosal Immunology|March 31, 2021

View abstract on PubMed

Summary

Endoplasmic reticulum membrane protein complex subunit 3 (Emc3) is crucial for intestinal secretory cells. Emc3 deficiency causes inflammation and organoid failure, but ER stress mitigation restores function.

Area of Science:

Gastroenterology
Cell Biology
Immunology

Background:

Intestinal secretory cells, like goblet and Paneth cells, are key for host defense.
The mechanisms governing their specification and maintenance for intestinal barrier integrity are not fully understood.

Purpose of the Study:

To investigate the role of endoplasmic reticulum membrane protein complex subunit 3 (Emc3) in intestinal exocrine secretory cell differentiation and function.
To elucidate the impact of Emc3 deficiency on intestinal homeostasis and disease susceptibility.

Main Methods:

Utilized genetic deletion of Emc3 in the intestinal epithelium.
Assessed mucus production, Paneth cell populations, gut microbiota composition, and susceptibility to DSS-induced colitis.
Investigated endoplasmic reticulum (ER) stress markers and organoid formation capacity.
Evaluated the therapeutic effect of tauroursodeoxycholate acid (TCA).

Main Results:

Emc3 deletion significantly reduced goblet cell mucus production and Paneth cell numbers.
Emc3 deficiency led to gut microbial dysbiosis, spontaneous intestinal inflammation, and increased colitis susceptibility.
Impaired Paneth cell stem cell niche function resulted in intestinal organoid culture failure.
Emc3 deficiency caused increased ER stress, which was alleviated by TCA, restoring secretory function and organoid formation.

Conclusions:

Emc3 is essential for the differentiation and function of intestinal exocrine secretory lineages.
Emc3 plays a critical role in maintaining intestinal mucosal homeostasis and barrier function.
Targeting ER stress presents a potential therapeutic strategy for Emc3-related intestinal dysfunction.