Published online Feb 21, 2020. doi: 10.3748/wjg.v26.i7.717
Peer-review started: November 18, 2019
First decision: December 23, 2019
Revised: January 7, 2020
Accepted: January 11, 2020
Article in press: January 11, 2020
Published online: February 21, 2020
Chronic constipation is a gastrointestinal functional disease that seriously harms physical and mental health and impacts the quality of life of patients. Its incidence rate is 2%-27%. Slow transit constipation (STC) is a common type of chronic functional constipation accounting for 10.3%-45.5% of such cases. At present, the most effective treatment for STC is still surgery, but it is more traumatic. We need to further explore the pathogenesis of the disease, through the intervention of gene or protein expression, to alleviate or prevent the occurrence of the disease.
There is no previous report which has linked constipation to the TGF-β/Smad signaling pathway and Tenascin-X (TNX) protein, and it is also the first time that TNX protein has been introduced into clinical research. The pathogenesis of STC is very complex, surgical treatment is effective, but it is traumatic. Therefore, it is necessary to find a new direction of treatment from the pathogenesis.
The main objective was to explore whether interstitial cells of Cajal (ICC) changes are related to transdifferentiation, and whether TNX protein can cause ICC changes through the TGF-β/Smad signaling pathway. At this stage, it was found that the expression level of the TNX protein was positively correlated with the TGF-β/Smad signaling pathway in the colon tissues of STC patients. Besides, ICC transdifferentiation rather than apoptosis or death was verified. Next, we need to confirm that the direction of transdifferentiation according to the morphological changes in ICC observed by electron microscopy and the patterns of specific expression factors after differentiation, such as α-SMA in the smooth muscle phenotype.
We collected surgical specimens of patients and tested them by different laboratory methods including qualitative and quantitative tests, such as colon immunohistochemistry, immunofluorescence staining, and Western blot. The data were compared between groups by the t-test, and correlation analysis was performed with the Pearson correlation coefficient.
The expression of the TNX protein in the colon of STC patients was significantly higher than that in the normal group by approximately 1.5-2 times. At the same time, it was found that the expression of Samd2/3 in the STC group was increased significantly, whereas the expression of the Smad7 inhibitor decreased, and these differences were correlated with the change in the TNX expression level. The results may provide a new experimental basis for the clinical treatment of STC.
The expression of the TNX protein is increased in the colon tissue of STC patients, which could affect the transdifferentiation of ICC by activating the TGF-β/Smad signaling pathway, upregulating the Smad2/3 excitatory factors, and downregulating the Smad7 inhibitory factor. The transdifferentiation of ICC could be inhibited by interfering with the signaling molecules in this pathway, thereby reducing or reversing the occurrence of STC, providing a new experimental basis for the clinical treatment of STC.
In the future, based on the cytological animal experiments, the changes in the TGF-β/Smad signaling pathway and the occurrence of STC under the two conditions need to be explored through gene knockout and overexpression of the TNX protein. We may be able to regulate the upstream and downstream signaling molecules of this pathway with targeting drugs, so as to alleviate or inhibit the development of STC.