miR-138-5p ameliorates intestinal barrier disruption caused by acute superior mesenteric vein thrombosis injury by inhibiting the NLRP3/HMGB1 axis.

Background: Acute superior mesenteric venous thrombosis (ASMVT) decreases junction-associated protein expression and intestinal epithelial cell numbers, leading to intestinal epithelial barrier disruption. Pyroptosis has also recently been found to be one of the important causes of mucosal barrier defects. However, the role and mechanism of pyroptosis in ASMVT are not fully understood. Methods: Differentially expressed microRNAs (miRNAs) in the intestinal tissues of ASMVT mice were detected by transcriptome sequencing (RNA-Seq). Gene expression levels were determined by RNA extraction and reverse transcription-quantitative PCR (RT-qPCR). Western blot and immunofluorescence staining analysis were used to analyze protein expression. H&E staining was used to observe the intestinal tissue structure. Cell Counting Kit-8 (CCK-8) and fluorescein isothiocyanate/propidine iodide (FITC/PI) were used to detect cell viability and apoptosis, respectively. Dual-luciferase reporter assays prove that miR-138-5p targets NLRP3. Results: miR-138-5p expression was downregulated in ASMVT-induced intestinal tissues. Inhibition of miR-138-5p promoted NLRP3-related pyroptosis and destroyed tight junctions between IEC-6 cells, ameliorating ASMVT injury. miR-138-5p targeted to downregulate NLRP3. Knockdown of NLRP3 reversed the inhibition of proliferation, apoptosis, and pyroptosis and the decrease in tight junction proteins caused by suppression of miR-138-5p; however, this effect was later inhibited by overexpressing HMGB1. miR-138-5p inhibited pyroptosis, promoted intestinal epithelial tight junctions and alleviated ASMVT injury-induced intestinal barrier disruption via the NLRP3/HMGB1 axis.

Transcription Factor TCF3 Promotes Macrophage-Mediated Inflammation and MMP Secretion in Abdominal Aortic Aneurysm by Regulating miR-143-5p /CCL20.

ABSTRACT: Damage to the abdominal aortic wall and the local inflammatory response are key factors resulting in abdominal aortic aneurysm (AAA) formation. During this process, macrophage polarization plays a key role. However, in AAA, the regulatory mechanism of macrophages is still unclear, and further research is needed. In this study, we found that the transcription factor TCF3 was expressed at low levels in AAA. We overexpressed TCF3 and found that TCF3 could inhibit MMP and inflammatory factor expression and promote M2 macrophage polarization, thereby inhibiting the progression of AAA. Knocking down TCF3 could promote M1 polarization and MMP and inflammatory factor expression. In addition, we found that TCF3 increased miR-143-5p expression through transcriptional activation of miR-143-5p , which further inhibited expression of the downstream chemokine CCL20 and promoted M2 macrophage polarization. Our research indicates that TCF3-mediated macrophage polarization plays a key regulatory role in AAA, complementing the role and mechanism of macrophages in the occurrence and development of AAA and providing a scientific basis for AAA treatment.

Visfatin inhibits colon cancer cell apoptosis and decreases chemosensitivity to 5­FU by promoting the SDF­1/CXCR4/Akt axis.

5­Fluorouracil (5­FU) is the preferred chemotherapeutic drug used in the treatment of colon cancer; however, drug resistance affects its clinical efficacy. Visfatin, an adipokine that promotes tumour development, has the potential to increase resistance to chemotherapy. The present study aimed to verify the effects of visfatin on the sensitivity of colon cancer cells to 5­FU and to elucidate the potential mechanisms involved. Tissue microarrays (TMAs) were used to analyse visfatin differential expression in normal colon and colon cancer tissues, and the data were further validated in vitro. Cell Counting Kit­8, clone formation, caspase­3/7 activity assays, as well as other analyses were used to verify the effects of visfatin on sensitivity to 5­FU. TMA and correlation analyses were used to predict and verify the correlation between visfatin and stromal cell­derived factor­1 (SDF­1). Rescue experiments and PI3K/Akt inhibitors were used to verify the role of the visfatin/SDF­1/Akt axis in the sensitivity of colon cancer cells to 5­FU. Visfatin was found to be highly expressed in colon cancer tissues and cell lines. Moreover, visfatin knockdown increased apoptosis, reduced cell proliferation and enhanced the chemosensitivity of DLD­1 and SW48 cells to 5­FU. A positive correlation between visfatin and SDF­1 was observed, with the knockdown of visfatin enhancing cell sensitivity to 5­FU chemotherapy by targeting the SDF­1/C­X­C chemokine receptor type 4 (CXCR4) axis. Furthermore, the Akt signalling pathway downstream of SDF­1/CXCR4 proved to be critical in the decreased sensitisation of colon cancer cells to 5­FU induced by visfatin. On the whole, the present study demonstrates that visatin can potentially decrease colon cancer cell apoptosis, promote proliferation and decrease colon cancer cell sensitivity to 5­FU via the visfatin/SDF­1/Akt axis.