Related Experiment Video

Updated: Dec 30, 2025

Author Spotlight: Enhancing Understanding and Treatment Strategies with the NEC-on-a-Chip Model
06:51

Author Spotlight: Enhancing Understanding and Treatment Strategies with the NEC-on-a-Chip Model

Published on: July 28, 2023

1.7K

Calcium/calmodulin-dependent protein kinase IV signaling pathway is upregulated in experimental necrotizing

Mashriq Alganabi1, Haitao Zhu1, Joshua S O'Connell1

  • 1Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON, M5G 1X8, Canada.

Pediatric Surgery International
|January 18, 2020
PubMed
Abstract

Insights

Necrotizing enterocolitis (NEC) involves increased calcium/calmodulin-dependent protein kinase IV (CaMKIV) expression and activation. This suggests CaMKIV may play a role in NEC development, warranting further investigation into its pathogenic mechanisms.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Pediatric Research

Background:

  • Calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation exacerbates intestinal injury and hinders epithelial cell proliferation in dextran sulfate sodium (DSS)-induced colitis models.
  • The specific role of CaMKIV in necrotizing enterocolitis (NEC) remains uncharacterized.

Purpose of the Study:

  • To investigate the expression and activation status of CaMKIV in a mouse model of experimental NEC.

Main Methods:

  • Experimental NEC was induced in C57BL/6 mouse pups (n=10) via hypoxia, formula gavage, and lipopolysaccharide exposure from postnatal days 5-9.
  • Control pups (n=10) were breastfed. Terminal ileum tissues were harvested on postnatal day 9 for histological scoring and assessment of CaMKIV, CREM, and IL17 gene expression, as well as CaMKIV and phosphorylated CaMKIV (pCaMKIV) protein levels.
  • Statistical analysis was performed using the Mann-Whitney U test.

Main Results:

  • Histological analysis confirmed intestinal injury in NEC mice, corroborated by elevated Interleukin-6 (IL6) levels.
  • Gene expression analysis revealed significant upregulation of CaMKIV, CREM, and IL17 in NEC mice compared to controls.
  • Western blot analysis demonstrated notably increased expression of phosphorylated CaMKIV (pCaMKIV), the active form, in the ileal tissue of NEC mice.

Conclusions:

  • CaMKIV expression and activation are significantly upregulated in experimental NEC.
  • These findings suggest that CaMKIV may be a contributing factor in the pathogenesis of NEC.
Keywords:
Calcium/calmodulin-dependent protein kinase IV (CaMKIV)IL17Necrotizing enterocolitis (NEC)pCaMKIV

More Related Videos

A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis08:42

A Novel Human Epithelial Enteroid Model of Necrotizing Enterocolitis

Published on: April 10, 2019

8.1K
In Vitro Apical-Out Enteroid Model of Necrotizing Enterocolitis09:11

In Vitro Apical-Out Enteroid Model of Necrotizing Enterocolitis

Published on: June 8, 2022

2.6K

Related Concept Videos

Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.9K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
9.7K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.7K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.1K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
8.2K
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.1K