Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells

Shi, Shuaishuai; Zhang, Yiqiang; Wen, Wenbin; Zhao, Yin′e; Sun, Lin

doi:10.3892/mmr.2016.5744

Cited by 8 publications

(8 citation statements)

References 25 publications

(20 reference statements)

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“…As the proinflammatory actions of TLR4 are frequently also associated with NF‐κB activation and prooxidant effects, inhibitory actions of melatonin on TLR4 are of particular mechanistic interest for the understanding of reducing inflammation. This mode of action by melatonin was repeatedly demonstrated and sometimes shown to be associated with inhibitions of NF‐κB and of inflammasome activation as well as upregulation of Nrf2 . These findings were obtained in different organs and models, under various conditions, from endotoxemia, ischemia/reperfusion and other forms of brain injury to chemically induced inflammation.…”

Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 79%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

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Melatonin is an immune modulator that displays both pro‐ and anti‐inflammatory properties. Proinflammatory actions, which are well documented by many studies in isolated cells or leukocyte‐derived cell lines, can be assumed to enhance the resistance against pathogens. However, they can be detrimental in autoimmune diseases. Anti‐inflammatory actions are of particular medicinal interest, because they are observed in high‐grade inflammation such as sepsis, ischemia/reperfusion, and brain injury, and also in low‐grade inflammation during aging and in neurodegenerative diseases. The mechanisms contributing to anti‐inflammatory effects are manifold and comprise various pathways of secondary signaling. These include numerous antioxidant effects, downregulation of inducible and inhibition of neuronal NO synthases, downregulation of cyclooxygenase‐2, inhibition of high‐mobility group box‐1 signaling and toll‐like receptor‐4 activation, prevention of inflammasome NLRP3 activation, inhibition of NF‐κB activation and upregulation of nuclear factor erythroid 2‐related factor 2 (Nrf2). These effects are also reflected by downregulation of proinflammatory and upregulation of anti‐inflammatory cytokines. Proinflammatory actions of amyloid‐β peptides are reduced by enhancing α‐secretase and inhibition of β‐ and γ‐secretases. A particular role in melatonin's actions seems to be associated with the upregulation of sirtuin‐1 (SIRT1), which shares various effects known from melatonin and additionally interferes with the signaling by the mechanistic target of rapamycin (mTOR) and Notch, and reduces the expression of the proinflammatory lncRNA‐CCL2. The conclusion on a partial mediation by SIRT1 is supported by repeatedly observed inhibitions of melatonin effects by sirtuin inhibitors or knockdown.

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Section: Downstream Factors Of Melatonin's Actions With Relevance To mentioning

confidence: 79%

Melatonin and inflammation—Story of a double‐edged blade

Hardeland

2018

Journal of Pineal Research

360

350

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“…Peritoneal inflammation plays an important role in mesothelial cell EMT 15 . It is believed that EMT is a pathological event responding to trauma and inflammatory insult.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells

Cheng

et al. 2018

Sci Rep

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Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we therefore investigated whether EMT can be affected by H2S in MCs. Rats were treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to produce PS, and NaHS (56 μg/kg.d) was given simultaneously. NaHS (56 μg/kg.d) reduced the deposition of collagen in the submesothelial zone compared with the PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in MCs featured as loss of ZO-1 and Cytokeratin, and increase of α-SMA, plasminogen activator inhibitor 1, fibronectin and TGF-β1 proteins. PD fluid also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well as the phosphorylation of Smad2/3 and Smad3. NaHS (50–300 μmol/L) reversed the above alterations with the optimal dose at 100 μmol/L. Thus, exogenous H2S improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated with the inhibition of inflammation and TGF-β1-Smad signal pathway.

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“…LPS is a major component of the outer wall of E. coli and induces epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells. [ 12 , 13 , 14 ] During EMT, the epithelial cells lose adhesion and close connections with adjacent cells and eventually convert to mesenchymal cells. EMT in peritoneal mesothelial cells initiates peritoneal fibrosis and is reversible [15] .…”

Section: Introductionmentioning

confidence: 99%

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

Peng

et al. 2019

Chinese Medical Journal

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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.

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Molecular mechanisms of melatonin in the reversal of LPS-induced EMT in peritoneal mesothelial cells

Cited by 8 publications

References 25 publications

Melatonin and inflammation—Story of a double‐edged blade

Melatonin and inflammation—Story of a double‐edged blade

Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells

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

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