scholarly journals Research on the Protective Effect of MiR-185-3p Mediated by Huangqin-Tang Decoction (HQT) on the Epithelial Barrier Function of Ulcerative Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Zhou Changlin ◽  
Zou Ying ◽  
Zhang Shuhua ◽  
Jiayang Zeng ◽  
Honggang Chi

Introduction. It has been reported that the traditional Chinese medicine Huangqin-Tang decoction (HQT) has a protective effect on the epithelial barrier function of ulcerative colitis, but its mechanism has not been fully clarified. This study intends to explore the protective mechanism of HQT in regulating microRNA (miRNA) for the first time. Methods. Based on the Balb/c mice ulcerative colitis model, the mice were given a gavage of 0.1 mL/10 g HQT every day for 7 days; on the 8th day, the colon of the mice was dissected, the length of the colon for the mice was measured, and the score was given based on this. Analysis of colonic mucosal injury was conducted by hematoxylin-eosin staining. Then, the differential miRNA was screened and sequenced in colon tissue using the HiSeq platform. And the differential miR-185-3p gene was verified by RT-PCR. Finally, the effects of HQT on miR-185-3p, occludin protein expression, and transepithelial electrical resistance (TEER) value were observed in combination with the CaCo2 intestinal epithelial cell model. Results. HQT treatment can alleviate the shortening of colon length and reverse the intestinal mucosal injury. miRNA sequencing of colonic tissue showed that miR-185-3p was significantly downregulated in the model group, while HQT could upregulate miR-185-3p, thereby affecting the myosin light chain kinase (MLCK)/myosin light chain phosphorylation (p-MLC) pathway and leading to increased expression of occludin protein, which ultimately protected the intestinal epithelial barrier function. Conclusion. HQT can protect colon epithelial barrier function by regulating miR-185-3p.

Epigenomics ◽  
2021 ◽  
Author(s):  
Bing Li ◽  
Yan Li ◽  
Lixiang Li ◽  
Yu Yu ◽  
Xiang Gu ◽  
...  

Aims: Few circRNAs have been thoroughly explored in ulcerative colitis (UC). Materials & methods: Microarrays and qualitative real-time PCR were used to detect and confirm dysregulated circRNAs associated with UC. Functional analysis was performed to explore the roles. Results: A total of 580 circRNAs and 87 miRNAs were simultaneously dysregulated in both inflamed and noninflamed UC colonic mucosa compared with healthy controls. Accordingly, hsa_circ_0001021 was significantly downregulated in patients with UC and was related to Mayo scores. Clinical samples and cell experiments revealed that hsa_circ_0001021 was expressed in epithelial cells and correlated with ZO-1, occludin and CLDN-2. Moreover, hsa_circ_0001021 sponged miR-224-5p to upregulate smad4 and increased ZO-1 and occludin. Conclusion: Hsa_circ_0001021 is related to UC severity and regulates epithelial barrier function via sponging miR-224-5p.


2019 ◽  
Vol 189 (9) ◽  
pp. 1763-1774 ◽  
Author(s):  
Artin Soroosh ◽  
Carl R. Rankin ◽  
Christos Polytarchou ◽  
Zulfiqar A. Lokhandwala ◽  
Ami Patel ◽  
...  

Marine Drugs ◽  
2019 ◽  
Vol 17 (8) ◽  
pp. 450 ◽  
Author(s):  
Song ◽  
Chen ◽  
Wang ◽  
Han ◽  
Zhang ◽  
...  

The effect of collagen peptides (CPs) in intestinal mucosal protection has been approved in both cell and animal models. However, its structure–activity relationship and efficient peptide sequences are unclear, which hinders the in-depth study of its action mechanism and relative nutraceuticals and pharmaceuticals development. In this work, size exclusion chromatography, cation-exchange chromatography, and RP-HPLC were used to separate Alaska pollock skin-derived collagen hydrolysates based on their molecular weight, charge property, and hydrophobicity. The intestinal epithelial barrier function (IEBF) protective effect of separated peptide fractions were evaluated by tumor necrosis factor (TNF)-α-induced Caco-2 cell model. Results indicated that lower molecular weight (500–1000 Da) and higher hydrophilicity of CPs were related to better IEBF protective effect. Two high-efficiency IEBF protective peptide sequences, GPSGPQGSR and GPSGLLGPK with the corresponding molecular weights of 841.41 Da and 824.38 Da, were subsequently identified by UPLC-QToF-MS/MS. Their IEBF protective ability are comparable or even better than the currently used intestinal health supplements glutamine and arginine. The present findings suggested that the hydrophilic CPs, with molecular weight between 500 Da to 1000 Da, should be preferred in IEBF protective peptides preparation. GPSGPQGSR and GPSGLLGPK might have the potential of being IEBF protective ingredients used in intestinal health supplements and drugs.


2017 ◽  
Vol 41 (5) ◽  
pp. 1924-1934 ◽  
Author(s):  
Akihiro Watari ◽  
Yuta Sakamoto ◽  
Kota Hisaie ◽  
Kazuki Iwamoto ◽  
Miho Fueta ◽  
...  

Background/Aims: Although proinflammatory cytokine–induced disruption of intestinal epithelial barrier integrity is associated with intestinal inflammatory disease, effective treatment for barrier dysfunction is lacking. Previously, we demonstrated that rebeccamycin alleviates epithelial barrier dysfunction induced by inflammatory cytokines in Caco-2 cell monolayers; however, the underlying mechanism remained unclear. Here, we investigated the mechanism by which rebeccamycin protects the epithelial barrier function of Caco-2 cells exposed to TNF-α. Methods: To confirm the epithelial barrier function of Caco-2 cell monolayers, transepithelial electrical resistance (TER) and paracellular permeability were measured. Production levels and localization of tight junction (TJ) proteins were analyzed by immunoblot and immunofluorescence, respectively. Phosphorylated myosin light chain (pMLC) and MLC kinase (MLCK) mRNA expression levels were determined by immunoblot and quantitative RT-PCR, respectively. Results: Rebeccamycin attenuated the TNF-α-induced reduction in TER and increase in paracellular permeability. Rebeccamycin increased claudin-5 expression, but not claudin-1, -2, -4, occludin or ZO-1 expression, and prevented the TNF-α-induced changes in ZO-1 and occludin localization. Rebeccamycin suppressed the TNF-α-induced increase in MLCK mRNA expression, thus suppressing MLC phosphorylation. The rebeccamycin-mediated reduction in MLCK production and protection of epithelial barrier function were alleviated by Chk1 inhibition. Conclusion: Rebeccamycin attenuates TNF-α-induced disruption of intestinal epithelial barrier integrity by inducing claudin-5 expression and suppressing MLCK production via Chk1 activation.


2002 ◽  
Vol 123 (4) ◽  
pp. 1179-1190 ◽  
Author(s):  
Kevin G.–E. Scott ◽  
Jonathon B. Meddings ◽  
David R. Kirk ◽  
Susan P. Lees–Miller ◽  
André G. Buret

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