The gene MKL1 contributes to the development of colitis, thus it may be a potential therapeutic target for the prevention of Inflammatory bowel disease (IBD).
Inflammatory bowel disease (IBD), including the two conditions ulcerative colitis and Crohn's disease, results in long-term inflammation of the gut and is associated with dysregulation of the immune system. However, it is notoriously difficult to determine the cause of IBD, although genetic and environmental factors are implicated. To better understand disease development, researchers have developed a mouse model in which gut inflammation is induced by addition of the chemical dextran sodium sulfate (DSS) to the drinking water of mice.
Ulcerative Colitis
Ulcerative colitis is characterized by bouts of diarrhea, bleeding per rectum and pain, which remits and relapses. Fulminant colitis is a possibility, which may require colectomy.
Advertisement
‘The overexpression of the gene MKL1 worsens the development of inflammatory bowel disease (IBD)-associated inflammation, this suggests that targeting of the protein or gene has potential for the treatment of IBD.’
Tweet it Now
Mice lacking the MKL1 protein, which shuttles between cytoplasm and nucleus serving as a transcriptional co-factor of serum response factor, develop less-severe inflammation in the IBD model than control animals. This suggested that MKL1 has a role in IBD disease development, but the details of this were unclear. Researchers at Tokyo Medical and Dental University (TMDU) built on this knowledge by generating mice overexpressing human MKL1 in specific white blood cells. They revealed that MKL1 causes the development of inflammation by controlling white blood cell functions.
The gut lining closest to the intestinal canal contains a layer of tissue including white blood cells known as macrophages, which are the scavengers of the immune system. These macrophages help maintain the gut equilibrium, and protect it from infection.
![Digestive Tract Ulcers Symptom Evaluation]( "Digestive Tract Ulcers Symptom Evaluation")
A break in the mucus membrane lining of the digestive tract results in ulcers.
The TMDU researchers showed MKL1 is expressed at higher levels in the macrophages of mice treated with DSS than untreated mice. This strongly suggested a role for macrophage MKL1 in the development of IBD.
The team then developed mice that expressed high levels of human MKL1 specifically in their lineage of macrophages, which are large white blood cells regulating the immune system.
"We noticed that these transgenic mice had fewer proportion of macrophages and more monocytes in the lining of their colon wall than control mice," explains Jianbo An, lead author of the study. "Intestinal macrophages suppress inflammation as a part of their defensive immune response."
"Microscopic examination of the colons of DSS-treated transgenic mice revealed destruction of the epithelium and severe ulceration," corresponding author Akinori Kimura says. "This was accompanied by a massive influx of inflammatory cells. The fulminant pathology may result from mitigated anti-inflammatory property of macrophages."
As the overexpression of MKL1 worsens the development of IBD-associated inflammation, this suggests that targeting of the protein or gene has potential for the treatment of IBD, which currently has no cure.
Source: Eurekalert
Digestive Tract Ulcers Symptom Evaluation
A break in the mucus membrane lining of the digestive tract results in ulcers.
Advertisement
The TMDU researchers showed MKL1 is expressed at higher levels in the macrophages of mice treated with DSS than untreated mice. This strongly suggested a role for macrophage MKL1 in the development of IBD.
The team then developed mice that expressed high levels of human MKL1 specifically in their lineage of macrophages, which are large white blood cells regulating the immune system.
"We noticed that these transgenic mice had fewer proportion of macrophages and more monocytes in the lining of their colon wall than control mice," explains Jianbo An, lead author of the study. "Intestinal macrophages suppress inflammation as a part of their defensive immune response."
"Microscopic examination of the colons of DSS-treated transgenic mice revealed destruction of the epithelium and severe ulceration," corresponding author Akinori Kimura says. "This was accompanied by a massive influx of inflammatory cells. The fulminant pathology may result from mitigated anti-inflammatory property of macrophages."
As the overexpression of MKL1 worsens the development of IBD-associated inflammation, this suggests that targeting of the protein or gene has potential for the treatment of IBD, which currently has no cure.
Source: Eurekalert
Inflammatory Bowel Disease
Inflammatory bowel disease involves chronic inflammation of the colon and small intestine. Symptoms include diarrhea, abdominal pain and weight loss.
Advertisement
 Irritable Bowel SyndromeIrritable bowel syndrome (IBS) causes recurrent abdominal pain or discomfort and a fluctuating disturbance in defecation. IBS is not life-threatening. | Advertisement
|
Advertisement
Recommended Reading
Latest Research News
The International Space Station will be used to carry out experiments seeking to improve understanding of incurable child brain tumors and the muscle aging process.
How many people in the UK have misophonia? In a representative sample study, most people had at least some irritation upon hearing trigger sounds.
Routine eye-checkups and mass screenings enable early diagnosis and treatment of glaucoma. Late-stage glaucoma diagnosis leads to blindness.
Brain plasticity following blindness leads to superior ability in sensing signals from the heart, which has implications for bodily awareness and emotional processing.
A group of scientists were awarded £1.3 million to create a new “point of care testing” kit that detects Alzheimer's disease biomarkers.