Matrine suppresses lipopolysaccharide-induced fibrosis in human peritoneal mesothelial cells by inhibiting the epithelial-mesenchymal transition

Abstract

Background:Peritoneal fibrosis is the primary reason that patients with end-stage renal disease (ESRD) have to cease peritoneal dialysis. Peritonitis caused by Gram-negative bacteria such as Escherichia coli (E. coli) were on the rise. We had previously shown that matrine inhibited the formation of biofilm by E. coli. However, the role of matrine on the epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells under chronic inflammatory conditions is still unknown.Methods:We cultured human peritoneal mesothelial cells (HPMCs) with lipopolysaccharide (LPS) to induce an environment that mimicked peritonitis and investigated whether matrine could inhibit LPS-induced EMT in these cells. In addition, we investigated the change in expression levels of the miR-29b and miR-129-5p.Results:We found that 10 μg/ml of LPS induced EMT in HPMCs. Matrine inhibited LPS-induced EMT in HPMCs in a dose-dependent manner. We observed that treatment with matrine increased the expression of E-cadherin (F = 50.993, P < 0.01), and decreased the expression of alpha-smooth muscle actin (F = 32.913, P < 0.01). Furthermore, we found that LPS reduced the expression levels of miR-29b and miR-129-5P in HPMCs, while matrine promoted the expression levels of miR-29b and miR-129-5P.Conclusions:Matrine could inhibit LPS-induced EMT in HPMCs and reverse LPS inhibited expressions of miR-29 b and miR-129-5P in HPMCs, ultimately reduce peritoneal fibrosis. These findings provide a potential theoretical basis for using matrine in the prevention and treatment of peritoneal fibrosis.

Differential expression and clinical significance of IGF2BP3 in peritoneal dialysate of patients with varying duration of peritoneal dialysis

“…FN is a noncollagenous glycoprotein with important biological Previous research indicated that FN is upregulated in PF, promoting epithelial-mesenchymal (EMT) in peritoneal mesothelial cells. 21 Our findings show a significant increase in FN expression in patients with more than 5 years of dialysis (p < 0.05), consistent with previous reports. Moreover, there was a positive correlation between IGF2BP3 and FN (r = 0.340, p = 0.030), further indicating a close relationship between IGF2BP3 and PF.…”

Elevated BCAA Suppresses the Development and Metastasis of Breast Cancer

“…The epithelial-to-mesenchymal transition (EMT) is a biological process strongly associated with tumor progression, invasion, and metastasis ( 39 , 40 ). As the concentration of BCAA increased in the culture medium, the expression of N-Cadherin, a key mesenchymal marker, dramatically decreased in LM2 cells ( Figure 6G ).…”

Research Progress on the Mechanism of Natural Product Ingredients in the Treatment of Uveitis

“…, matrine has antibacterial, anti-inflammatory, antitumor, and antiarrhythmia effects. Matrine has an inhibitory effect on the inflammatory reactions caused by liposaccharides (LPS) [ 23 , 24 ] LPS, a component of the cell wall of gram-negative bacteria, acts on the Toll-like receptors 4 (TLR4) receptor to induce myeloid differentiation factor88 (MyD88) recruitment, followed by activation of nuclear factor kappa-B (NF- κ B) through a series of phosphorylation cascades [ 25 ]. After the inflammatory factors destroy the blood-aqueous barrier or blood-retinal barrier, some macromolecular protein substances and cells in the blood infiltrate into the interstitial or intracavity of the eye (anterior chamber or vitreous body), giving rise to different degrees of tissue damage [ 26 ].…”

“…Extracted from the dried root of Sophora flavescens, Alt., matrine has antibacterial, anti-inflammatory, antitumor, and antiarrhythmia effects. Matrine has a good inhibitory effect on the inflammatory reaction caused by LPS [17,18]. Liposaccharides (LPS), a component of the cell wall of gram-negative bacteria, acts on the TLR4 receptor to induce MyD88 recruitment, followed by activation of NF-κB through a series of phosphorylation cascades [19].…”