Thermal Injury Effects on Intestinal Crypt Cell Proliferation and Death are Cell- Position Dependent

We examined the effects of thermal injury on intestinal epithelial cell proliferation and death. We recorded histologically identifiable mitotic and apoptotic crypt cells in relation to cell position after a 60% full thickness cutaneous thermal injury in the rat. The injury significantly reduced mitosis (0.53 ± 0.11 vs. 1.50 ± 0.70, P < 0.05) at cell positions 4–6, stem cells, 6 h after injury. A similar reduction in mitosis (1.13 ± 0.59 vs. 3.50 ± 0.80, P < 0.05) was observed at higher cell positions 7–9 12 h after injury, indicating a positional cell shift. In addition, a significant increase in the number of apoptotic bodies occurred at cell positions 7–9(2.32 ± 0.87 vs. 0.13 ± 0.22, P < 0.05) and 10–12 (2.2 ± 0.12 vs. 0.00, P< 0.05) 6 h after injury. Thermal injury-induced alterations in mitotic and apoptotic activities were transient since crypts recovered with a moderate increase in mitotic activity 24 h after injury. In control and thermal-injury rats 24 h after injury, crypt cell mitosis and apoptosis did not differ significantly. This demonstrates that cutaneous thermal injury causes a transient suppression of mitosis as well as induction of apoptosis in a cell position-dependent manner in the small intestinal crypt.

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An Active Fraction of Trillium tschonoskii Promotes the Regeneration of Intestinal Epithelial Cells After Irradiation

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.745412 ◽

2021 ◽

Vol 9 ◽

Author(s):

Feiling Song ◽

Sihan Wang ◽

Xu Pang ◽

Zeng Fan ◽

Jie Zhang ◽

...

Keyword(s):

Cell Proliferation ◽

Crypt Cell ◽

Oral Drug ◽

Epithelial Cell Line ◽

Intestinal Epithelial ◽

Active Fraction ◽

Intestinal Crypt ◽

Crypt Cell Proliferation ◽

Trillium Tschonoskii ◽

Intestinal Crypt Cell

Despite significant scientific advances toward the development of safe and effective radiation countermeasures, no drug has been approved for use in the clinic for prevention or treatment of radiation-induced acute gastrointestinal syndrome (AGS). Thus, there is an urgent need to develop potential drugs to accelerate the repair of injured intestinal tissue. In this study, we investigated that whether some fractions of Traditional Chinese Medicine (TCM) have the ability to regulate intestinal crypt cell proliferation and promotes crypt regeneration after radiation. By screening the different supplements from a TCM library, we found that an active fraction of the rhizomes of Trillium tschonoskii Maxim (TT), TT-2, strongly increased the colony-forming ability of irradiated rat intestinal epithelial cell line 6 (IEC-6) cells. TT-2 significantly promoted the proliferation and inhibited the apoptosis of irradiated IEC-6 cells. Furthermore, in a small intestinal organoid radiation model, TT-2 promoted irradiated intestinal organoid growth and increased Lgr5+ intestinal stem cell (ICS) numbers. More importantly, the oral administration of TT-2 remarkably enhanced intestinal crypt cell proliferation and promoted the repair of the intestinal epithelium of mice after abdominal irradiation (ABI). Mechanistically, TT-2 remarkably activated the expression of ICS-associated and proliferation-promoting genes and inhibited apoptosis-related gene expression. Our data indicate that active fraction of TT can be developed into a potential oral drug for improving the regeneration and repair of intestinal epithelia that have intestinal radiation damage.

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Effect of enzyme supplementation of a rye-based diet on xylanase activity in the small intestine of broilers, on intestinal crypt cell proliferation and on nutrient digestibility and growth performance of the birds

British Poultry Science ◽

10.1080/00071660120121508 ◽

2002 ◽

Vol 43 (2) ◽

pp. 274-282 ◽

Cited By ~ 54

Author(s):

S.S.P. Silva ◽

R.R. Smithard

Keyword(s):

Cell Proliferation ◽

Small Intestine ◽

Growth Performance ◽

Xylanase Activity ◽

Nutrient Digestibility ◽

Crypt Cell ◽

Intestinal Crypt ◽

Crypt Cell Proliferation ◽

Enzyme Supplementation ◽

Intestinal Crypt Cell

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Glucagon-Like Peptide-2 Activates β-Catenin Signaling in the Mouse Intestinal Crypt: Role of Insulin-Like Growth Factor-I

Endocrinology ◽

10.1210/en.2007-0561 ◽

2007 ◽

Vol 149 (1) ◽

pp. 291-301 ◽

Cited By ~ 56

Author(s):

Philip E. Dubé ◽

Katherine J. Rowland ◽

Patricia L. Brubaker

Keyword(s):

Cell Proliferation ◽

Nuclear Translocation ◽

Glycogen Synthase ◽

Crypt Cell ◽

Acute Administration ◽

Intestinal Crypt ◽

Crypt Cell Proliferation ◽

Igf I ◽

Glucagon Like Peptide ◽

Crypt Cells

Chronic administration of glucagon-like peptide-2 (GLP-2) induces intestinal growth and crypt cell proliferation through an indirect mechanism requiring IGF-I. However, the intracellular pathways through which IGF-I mediates GLP-2-induced epithelial tropic signaling remain undefined. Because β-catenin and Akt are important regulators of crypt cell proliferation, we hypothesized that GLP-2 activates these signaling pathways through an IGF-I-dependent mechanism. In this study, fasted mice were administered Gly2-GLP-2 or LR3-IGF-I (positive control) for 0.5–4 h. Nuclear translocation of β-catenin in non-Paneth crypt cells was assessed by immunohistochemistry and expression of its downstream proliferative markers, c-myc and Sox9, by quantitative RT-PCR. Akt phosphorylation and activation of its targets, glycogen synthase kinase-3β and caspase-3, were determined by Western blot. IGF-I receptor (IGF-IR) and IGF-I signaling were blocked by preadministration of NVP-AEW541 and through the use of IGF-I knockout mice, respectively. We found that GLP-2 increased β-catenin nuclear translocation in non-Paneth crypt cells by 72 ± 17% (P < 0.05) and increased mucosal c-myc and Sox9 mRNA expression by 90 ± 20 and 376 ± 170%, respectively (P < 0.05–0.01), with similar results observed with IGF-I. This effect of GLP-2 was prevented by blocking the IGF-IR as well as ablation of IGF-I signaling. GLP-2 also produced a time- and dose-dependent activation of Akt in the intestinal mucosa (P < 0.01), most notably in the epithelium. This action was reduced by IGF-IR inhibition but not IGF-I knockout. We concluded that acute administration of GLP-2 activates β-catenin and proliferative signaling in non-Paneth murine intestinal crypt cells as well as Akt signaling in the mucosa. However, IGF-I is required only for the GLP-2-induced alterations in β-catenin.

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Dysregulation of intestinal crypt cell proliferation and villus cell migration in mice lacking Krüppel-like factor 9

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00013.2007 ◽

2007 ◽

Vol 292 (6) ◽

pp. G1757-G1769 ◽

Cited By ~ 35

Author(s):

Frank A. Simmen ◽

Rijin Xiao ◽

Michael C. Velarde ◽

Rachel D. Nicholson ◽

Margaret T. Bowman ◽

...

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Cell Migration ◽

Cell Fate ◽

Crypt Cell ◽

Cell Renewal ◽

Crypt Cell Proliferation ◽

Villus Cell ◽

Null Mutant Mice ◽

Intestinal Crypt Cell

Krüppel-like factor 9 (Klf9), a zinc-finger transcription factor, is implicated in the control of cell proliferation, cell differentiation, and cell fate. Using Klf9-null mutant mice, we have investigated the involvement of Klf9 in intestine crypt-villus cell renewal and lineage determination. We report the predominant expression of Klf9 gene in small and large intestine smooth muscle (muscularis externa). Jejunums null for Klf9 have shorter villi, reduced crypt stem/transit cell proliferation, and altered lineage determination as indicated by decreased and increased numbers of goblet and Paneth cells, respectively. A stimulatory role for Klf9 in villus cell migration was demonstrated by bromodeoxyuridine labeling. Results suggest that Klf9 controls the elaboration, from intestine smooth muscle, of molecular mediator(s) of crypt cell proliferation and lineage determination and of villus cell migration.

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