Anti-fibrotic effect of Sedum sarmentosum Bunge extract in kidneys via the hedgehog signaling pathway

Bai, Yongheng; Wu, Cunzao; Hong, Weilong; Zhang, Xing; Liu, Leping; Chen, Bicheng

doi:10.3892/mmr.2017.6628

Cited by 8 publications

(5 citation statements)

References 30 publications

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“…In the absence of extracellular osmolytes, E-cadherin, epithelial cell marker, was abundantly localized to the plasma membrane. The expression of α-SMA, a mesenchymal cell marker was rarely detected, which is consistent with previous studies investigating the induction of EMT using NRK-52E cells [ 35 – 37 ]. When the cells were stimulated by hyperosmotic stress for 12 h, the expression of E-cadherin was markedly decreased, and the expression of α-SMA was dramatically increased in the cytoplasm in a mannitol-dose-dependent manner ( Fig 1A ).…”

Section: Resultssupporting

confidence: 91%

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Hyperosmotic stress induces epithelial-mesenchymal transition through rearrangements of focal adhesions in tubular epithelial cells

2021

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Epithelial-mesenchymal transition (EMT) of tubular epithelial cells is a hallmark of renal tubulointerstitial fibrosis and is associated with chronic renal injury as well as acute renal injury. As one of the incidences and risk factors for acute renal injury, increasing the osmolality in the proximal tubular fluid by administration of intravenous mannitol has been reported, but the detailed mechanisms remain unclear. Hyperosmotic conditions caused by mannitol in the tubular tissue may generate not only osmotic but also mechanical stresses, which are known to be able to induce EMT in epithelial cells, thereby contributing to renal injury. Herein, we investigate the effect of hyperosmolarity on EMT in tubular epithelial cells. Normal rat kidney (NRK)-52E cells were exposed to mannitol-induced hyperosmotic stress. Consequently, the hyperosmotic stress led to a reduced expression of the epithelial marker E-cadherin and an enhanced expression of the mesenchymal marker, α-smooth muscle actin (α-SMA), which indicates an initiation of EMT in NKR-52E cells. The hyperosmotic condition also induced time-dependent disassembly and rearrangements of focal adhesions (FAs) concomitant with changes in actin cytoskeleton. Moreover, prevention of FAs rearrangements by cotreatment with Y-27632, a Rho-associated protein kinase inhibitor, could abolish the effects of hyperosmotic mannitol treatment, thus attenuating the expression of α-SMA to the level in nontreated cells. These results suggest that hyperosmotic stress may induce EMT through FAs rearrangement in proximal tubular epithelial cells.

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Section: Resultssupporting

confidence: 91%

“…previous studies investigating the induction of EMT using NRK-52E cells [35][36][37]. When the cells were stimulated by hyperosmotic stress for 12 h, the expression of E-cadherin was markedly decreased, and the expression of α-SMA was dramatically increased in the cytoplasm in a mannitol-dose-dependent manner (Fig 1A).…”

Section: Plos Onementioning

confidence: 65%

Hyperosmotic stress induces epithelial-mesenchymal transition through rearrangements of focal adhesions in tubular epithelial cells

2021

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“…no. YYR336; Shaanxi Yongyuan Biotechnology Co., Ltd., Shaanxi, China) was extracted in accordance with a previously described method [20]. SSB (82.50% purity) was purchased from Xi'an Yuze Biological Technology Co., Ltd. (Xi'an, China) and identified by Professor Yi Fu at the Department of Pharmacognosy, Yunnan Chinese Medical University.…”

Section: Ssb Extract Preparationmentioning

confidence: 99%

RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

Hao

Liu

et al. 2020

BMC Complement Med Ther

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Background: Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)induced acute liver injury in mice and the mechanism of such effects.Methods: Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 μg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice.Results: Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h.Conclusions: S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.

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“…Other authors demonstrated that SSBE has marked effects against renal fibrosis (Bai et al, 2014a; Bai et al, 2014b), down-regulating hedgehog signaling pathway (which promotes renal fibrogenesis fostering the formation of myofibroblasts from different cell types through an EMT process). SSBE also reduced the ECM accumulation and angiogenesis (Bai et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition

et al. 2019

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Epithelial-to-mesenchymal transition (EMT) is a self-regulated physiological process required for tissue repair that, in non-controled conditions may lead to fibrosis, angiogenesis, loss of normal organ function or cancer. Although several molecular pathways involved in EMT regulation have been described, this process does not have any specific treatment. This article introduces a systematic review of effective natural plant compounds and their extract that modulates the pathological EMT or its deleterious effects, through acting on different cellular signal transduction pathways both in vivo and in vitro . Thereby, cryptotanshinone, resveratrol, oxymatrine, ligustrazine, osthole, codonolactone, betanin, tannic acid, gentiopicroside, curcumin, genistein, paeoniflorin, gambogic acid and Cinnamomum cassia extracts inhibit EMT acting on transforming growth factor-β (TGF-β)/Smads signaling pathways. Gedunin, carnosol, celastrol, black rice anthocyanins, Duchesnea indica , cordycepin and Celastrus orbiculatus extract downregulate vimectin, fibronectin and N-cadherin. Sulforaphane, luteolin, celastrol, curcumin, arctigenin inhibit β-catenin signaling pathways. Salvianolic acid-A and plumbagin block oxidative stress, while honokiol, gallic acid, piperlongumine, brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL, TWIST and ZEB. Plectranthoic acid, resveratrol, genistein, baicalin, polyphyllin I, cairicoside E, luteolin, berberine, nimbolide, curcumin, withaferin-A, jatrophone, ginsenoside-Rb1, honokiol, parthenolide, phoyunnanin-E, epicatechin-3-gallate, gigantol, eupatolide, baicalin and baicalein and nitidine chloride inhibit EMT acting on other signaling pathways (SIRT1, p38 MAPK, NFAT1, SMAD, IL-6, STAT3, AQP5, notch 1, PI3K/Akt, Wnt/β-catenin, NF-κB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by the natural compounds of plant, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compounds to modulate EMT and its deleterious effects. Overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.

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Anti-fibrotic effect of Sedum sarmentosum Bunge extract in kidneys via the hedgehog signaling pathway

Cited by 8 publications

References 30 publications

Hyperosmotic stress induces epithelial-mesenchymal transition through rearrangements of focal adhesions in tubular epithelial cells

Hyperosmotic stress induces epithelial-mesenchymal transition through rearrangements of focal adhesions in tubular epithelial cells

RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression

Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition

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