Molecular regulation mechanism of intestinal stem cells in mucosal injury and repair in ulcerative colitis

Abstract

Ulcerative colitis (UC) is a chronic nonspecific inflammatory disease with complex causes. The main pathological changes were intestinal mucosal injury. Leucine-rich repeat-containing G protein coupled receptor 5 (LGR5)-labeled small intestine stem cells (ISCs) were located at the bottom of the small intestine recess and inlaid among Paneth cells. LGR5+ small ISCs are active proliferative adult stem cells, and their self-renewal, proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases. The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs. More importantly, the surviving stem cells after intestinal mucosal injury accelerate division, restore the number of stem cells, multiply and differentiate into mature intestinal epithelial cells, and repair the damaged intestinal mucosa. Therefore, in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling

“…Active Lgr5 + ISCs, located at the base of intestinal crypts, are responsible for regenerating the entire epithelial lineage under normal conditions and, thereby, play a critical role in maintaining intestinal homoeostasis [ 2 , 39 ]. The ISC niche exhibits high plasticity, with quiescent “+4 ISCs” rapidly regenerating after injury [ 16 , 40 ]. Our results demonstrated that Cldn-7 deficiency inhibits the stemness of active Lgr5 + stem cells and maybe activate the proliferation of Bmi1 + reserve stem cells.…”

“…The intestinal epithelium also rapidly regenerates in response to acute injury. Once damaged, the intestinal epithelium undergoes epithelial repair, in which ISCs activate, proliferate, and differentiate to restore the epithelium [ 14 – 16 ]. Acute inflammation has been shown to eradicate Lgr5 + ISCs in the small intestine and colon; this depletion of stem cells can delay or inhibit the regeneration of the damaged intestinal epithelium [ 17 , 18 ].…”

Advancements in hydrogel-based drug delivery systems for the treatment of inflammatory bowel disease: a review

“…One potential target for this purpose is leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5 + ) intestinal stem cells (ISCs) with self-renewal capability and high differentiation potential, which play essential roles in repairing damaged mucosa. 239,240 Other therapies such as mesenchymal stem cells, 241 exosomes, 242 and organoid transplantation 243 are also being gradually explored but face limitations due to nutritional supply issues, immune system attacks or low accumulation at the target site. According to the results of cell invasion and scratching experiments in Fig.…”