Phospholipase A2 stimulation of rat intestinal epithelial cell (IEC-6) migration

The effect of phospholipase A2 (PLA2) on intestinal epithelial cell migration was investigated using an in vitro wounding model of confluent monolayers of IEC-6. PLA2 (0.001-2 U/ml) enhanced IEC-6 cell migration in a dose dependent manner. Addition of 4-bromophenacyl bromide (BPB) (a PLA2 inhibitor) to PLA2 completely blocked the migration-promoting effect. However, addition of piroxicam (a cyclooxygenase inhibitor) or nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no influence on the effect. Lysophosphatidylcholine (lysoPC) (0.01-5,000 ng/ml), one of the products of phosphatidylcholine by PLA2, dose-dependently enhanced IEC-6 cell migration as well. A combination of PsLA2 (1 U/ml) and lysoPC (1,000 ng/ml) had no additive effect or migration. Moreover, the migration-promoting effect of PLA2 that was blocked by BPB was recovered by lysoPC. After pretreatment of IEC-6 cells with replication-inhibiting doses of mitomycin C, the enhanced migration induced by PLA2 or lysoPC was still observed. These observations suggest that PLA2 may, independently of proliferation, enhance intestinal epithelial cell migration mainly via lysoPC.

Download Full-text

Ursodeoxycholic acid protects against intestinal barrier breakdown by promoting enterocyte migration via EGFR- and COX-2-dependent mechanisms

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00354.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. G259-G271 ◽

Cited By ~ 15

Author(s):

Jamie M. Golden ◽

Oswaldo H. Escobar ◽

Michelle V. L. Nguyen ◽

Michael U. Mallicote ◽

Patil Kavarian ◽

...

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Ursodeoxycholic Acid ◽

Intestinal Epithelial Cell ◽

Growth Factor Receptor ◽

Intestinal Barrier ◽

Intestinal Epithelial ◽

Epithelial Cell Migration ◽

Cox 2

The intestinal barrier is often disrupted in disease states, and intestinal barrier failure leads to sepsis. Ursodeoxycholic acid (UDCA) is a bile acid that may protect the intestinal barrier. We hypothesized that UDCA would protect the intestinal epithelium in injury models. To test this hypothesis, we utilized an in vitro wound-healing assay and a mouse model of intestinal barrier injury. We found that UDCA stimulates intestinal epithelial cell migration in vitro, and this migration was blocked by inhibition of cyclooxygenase 2 (COX-2), epidermal growth factor receptor (EGFR), or ERK. Furthermore, UDCA stimulated both COX-2 induction and EGFR phosphorylation. In vivo UDCA protected the intestinal barrier from LPS-induced injury as measured by FITC dextran leakage into the serum. Using 5-bromo-2′-deoxyuridine and 5-ethynyl-2′-deoxyuridine injections, we found that UDCA stimulated intestinal epithelial cell migration in these animals. These effects were blocked with either administration of Rofecoxib, a COX-2 inhibitor, or in EGFR-dominant negative Velvet mice, wherein UDCA had no effect on LPS-induced injury. Finally, we found increased COX-2 and phosphorylated ERK levels in LPS animals also treated with UDCA. Taken together, these data suggest that UDCA can stimulate intestinal epithelial cell migration and protect against acute intestinal injury via an EGFR- and COX-2-dependent mechanism. UDCA may be an effective treatment to prevent the early onset of gut-origin sepsis. NEW & NOTEWORTHY In this study, we show that the secondary bile acid ursodeoxycholic acid stimulates intestinal epithelial cell migration after cellular injury and also protects the intestinal barrier in an acute rodent injury model, neither of which has been previously reported. These effects are dependent on epidermal growth factor receptor activation and downstream cyclooxygenase 2 upregulation in the small intestine. This provides a potential treatment for acute, gut-origin sepsis as seen in diseases such as necrotizing enterocolitis.

Download Full-text

M1846 5-Hydroxytryptamine Stimulates In Vitro Intestinal Epithelial Cell Migration

Gastroenterology ◽

10.1016/s0016-5085(10)61989-0 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-431

Author(s):

Lizbeth Lockwood ◽

Iva Sovadinova ◽

Stephanie N. Spohn ◽

Mark M. Kadrofske

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Intestinal Epithelial Cell ◽

Intestinal Epithelial ◽

Epithelial Cell Migration

Download Full-text

Attenuation of Intestinal Epithelial Cell Migration During Cryptosporidium parvum Infection Involves Parasite Cdg7_FLc_1030 RNA-Mediated Induction and Release of Dickkopf-1

The Journal of Infectious Diseases ◽

10.1093/infdis/jiy299 ◽

2018 ◽

Vol 218 (8) ◽

pp. 1336-1347 ◽

Cited By ~ 2

Author(s):

Zhenping Ming ◽

Yang Wang ◽

Ai-Yu Gong ◽

Xin-Tian Zhang ◽

Min Li ◽

...

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Cryptosporidium Parvum ◽

Intestinal Epithelial Cell ◽

Intestinal Epithelial ◽

Epithelial Cell Migration ◽

Dickkopf 1

Download Full-text

UNC‐45A is a novel regulator of the intestinal epithelial cell migration

The FASEB Journal ◽

10.1096/fasebj.2021.35.s1.03484 ◽

2021 ◽

Vol 35 (S1) ◽

Author(s):

Susana Lechuga ◽

Andrei Ivanov

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Intestinal Epithelial Cell ◽

Intestinal Epithelial ◽

Epithelial Cell Migration

Download Full-text

Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration

AJP Cell Physiology ◽

10.1152/ajpcell.2000.278.2.c303 ◽

2000 ◽

Vol 278 (2) ◽

pp. C303-C314 ◽

Cited By ~ 69

Author(s):

Jian-Ying Wang ◽

Jian Wang ◽

Vera A. Golovina ◽

Li Li ◽

Oleksandr Platoshyn ◽

...

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Driving Force ◽

Intestinal Epithelial Cell ◽

Delayed Rectifier ◽

Intestinal Epithelial ◽

Voltage Gated ◽

Epithelial Cell Migration ◽

Channel Expression ◽

Exogenous Spermidine

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential ( E m) that regulates cytoplasmic free Ca2+ concentration ([Ca2+]cyt) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E m, and [Ca2+]cyt in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E m in DFMO-treated cells decreased [Ca2+]cyt as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E m, and [Ca2+]cyt but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4-aminopyridine, 1–5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+]cyt by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.

Download Full-text