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Related Concept Videos

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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Stem cells are undifferentiated cells that divide and produce more stem cells or progenitor cells that differentiate into mature, specialized cell types. All the cells in the body are generated from stem cells in the early embryo, but small populations of stem cells are also present in many adult tissues including the bone marrow, brain, skin, and gut. These adult stem cells typically produce the various cell types found in that tissue—to replace cells that are damaged or to continuously...
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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Intestinal Epithelial Regeneration in Response to Ionizing Irradiation
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Gelsolin regulates intestinal stem cell regeneration and Th17 cellular function.

Jicong Du1, Lan Fang1, Yuedong Wang1,2

  • 1Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800 Xiangyin Road, Shanghai, 200433, P.R. China.

Cell Communication and Signaling : CCS
|October 30, 2024
PubMed
Summary

Gelsolin is crucial for intestinal stem cell regeneration after injury. It maintains Th17 cell function, promoting gut healing and protecting against conditions like colitis.

Keywords:
Gelsolin (Gelsolin)IL-17 signaling pathwayIR induced intestinal injuryIntestinal stem cells (ISCs)T helper cells 17 (Th17 cells)

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Area of Science:

  • Gastroenterology
  • Immunology
  • Cell Biology

Background:

  • Intestinal stem cells (ISCs) are vital for maintaining gut homeostasis and repairing damage.
  • Gelsolin's role in ISC function and intestinal injury response is not well understood.

Purpose of the Study:

  • To investigate the function of Gelsolin in intestinal injury and regeneration.
  • To elucidate the mechanism by which Gelsolin influences ISC function and gut repair.

Main Methods:

  • Ionizing radiation (IR) and DSS-induced colitis models in Gelsolin knockout (KO) mice.
  • Intestinal organoid culture and co-culture systems.
  • RNA sequencing, RT-PCR, and flow cytometry analysis.
  • Investigated the p-STAT3/RORγt signaling axis.

Main Results:

  • Gelsolin KO mice exhibited increased radiosensitivity, aggravated intestinal damage, and reduced ISC numbers post-IR.
  • Gelsolin deletion impaired ISC function and inhibited Th17 cell differentiation, down-regulating the IL-17 signaling pathway.
  • Recombinant IL-17A ameliorated IR-induced injury and promoted ISC regeneration.
  • Gelsolin deficiency affected Th17 cell functionality via the p-STAT3/RORγt axis.
  • Th17 cells enhanced self-renewal in Gelsolin-deficient organoids.
  • Gelsolin demonstrated protective effects against DSS-induced colitis.

Conclusions:

  • Gelsolin is essential for intestinal regeneration after injury, particularly by supporting ISC function.
  • Gelsolin maintains ISC regeneration by sustaining Th17 cell function through the p-STAT3/RORγt pathway.
  • Gelsolin plays a protective role in various forms of intestinal injury, including colitis.