Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats

Sheen, Jiunn‐Ming; Chen, Yu-Chieh; Hsu, Meng‐Hsiang; Tain, You‐Lin; Huang, Ying‐Hsien; Tiao, Mao‐Meng; Li, Shih-Wen; Huang, Laura

doi:10.3390/ijms17081365

Cited by 24 publications

(7 citation statements)

References 42 publications

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“…Knockdown of Y1 receptor attenuated the inhibitory effects of Dex on the proliferation ability of MC3T3-E1 cells (Figure 2D). Activation of caspases has been shown to contribute to apoptosis in various types of cells [21,22]. Thus, we evaluated cell apoptosis by detecting the levels of cleaved caspase 3 and cleaved caspase 9, two key molecules involved in apoptosis process.…”

Section: Resultsmentioning

confidence: 99%

Neuropeptide Y1 Receptor Regulates Glucocorticoid-Induced Inhibition of Osteoblast Differentiation in Murine MC3T3-E1 Cells via ERK Signaling

Zhu

et al. 2016

IJMS

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High dose glucocorticoid (GC) administration impairs the viability and function of osteoblasts, thus causing osteoporosis and osteonecrosis. Neuropeptide Y1 receptor (Y1 receptor) is expressed in bone tissues and cells, and regulates bone remodeling. However, the role of Y1 receptor in glucocorticoid-induced inhibition of osteoblast differentiation remains unknown. In the present study, osteoblastic cell line MC3T3-E1 cultured in osteogenic differentiation medium was treated with or without of 10−7 M dexamethasone (Dex), Y1 receptor shRNA interference, Y1 receptor agonist [Leu31, Pro34]-NPY, and antagonist BIBP3226. Cell proliferation and apoptosis were assessed by cell counting kit-8 (CCK-8) assay and cleaved caspase expression, respectively. Osteoblast differentiation was evaluated by Alizarin Red S staining and osteogenic marker gene expressions. Protein expression was detected by Western blot analysis. Dex upregulated the expression of Y1 receptor in MC3T3-E1 cells associated with reduced osteogenic gene expressions and mineralization. Blockade of Y1 receptor by shRNA transfection and BIBP3226 significantly attenuated the inhibitory effects of Dex on osteoblastic activity. Y1 receptor signaling modulated the activation of extracellular signal-regulated kinases (ERK) as well as the expressions of osteogenic genes. Y1 receptor agonist inhibited ERK phosphorylation and osteoblast differentiation, while Y1 receptor blockade exhibited the opposite effects. Activation of ERK signaling by constitutive active mutant of MEK1 (caMEK) abolished Y1 receptor-mediated Dex inhibition of osteoblast differentiation in MC3T3-E1 cells. Taken together, Y1 receptor regulates Dex-induced inhibition of osteoblast differentiation in murine MC3T3-E1 cells via ERK signaling. This study provides a novel role of Y1 receptor in the process of GC-induced suppression in osteoblast survival and differentiation.

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Section: Resultsmentioning

confidence: 99%

Neuropeptide Y1 Receptor Regulates Glucocorticoid-Induced Inhibition of Osteoblast Differentiation in Murine MC3T3-E1 Cells via ERK Signaling

Zhu

et al. 2016

IJMS

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“…An important finding of our study is the degenerative changes in the later stages of the experiment of the muscular membrane of the wall of the common bile duct. Experiments have shown that damage to the muscular layer of the bile duct leads to the development of liver cirrhosis [16,19,28,33] and even hepatocellular carcinoma [1,30]. Significant collagen deposition, portal fibrosis, periductal edema, lymphocytic inflammation, dilatation of all bile ducts, blind end of small bile ducts, cholestasis (bile corks), increased systemic oxidative stress, and fibrosis were observed in rats after ligature was applied to the common bile duct, which eventually leads to liver cirrhosis [15,32].…”

Section: Discussionmentioning

confidence: 99%

Morphological features of the wall of common bile duct under the conditions of experimental opioid exposure

2020

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The morphological condition of the bile ducts remains one of the most important problems of modern medical science. In order to obtain an analgesic effect in patients with acute cholangitis, opioids are often used. However, information on the effectiveness of opioids in the treatment of pathological conditions of the bile ducts is contradictory. The rapidly progressive destruction of the intrahepatic bile ducts associated with the use of narcotic agents has been described. Further study of the effect of opioids on the structural organization of the common bile duct is relevant. In order to establish the morphological state of the common bile duct under conditions of long-term opioid exposure, a study was performed on 24 sexually mature white male rats, aged 3.5-5.0 months and weighing 180-200 g, which were injected intramuscularly with Nalbuphine for 6 weeks. The study material is represented by histological specimens of the common bile duct of white rats. The “Aver Media” computer system was used to photograph microspecimens. The “ImageJ” computer program was used to measure the diameter of the lumen and the wall thickness of the common bile duct. After 2 weeks of Nalbuphine administration to white rats, plethora of wall microvessels and a significant increase in the longitudinal diameter of the lumen of the common bile duct were observed. After 4 weeks of the experiment, the common bile duct was dilated, the transverse and longitudinal diameters of its lumen almost doubled, pathological changes in its wall had all the signs of inflammation. In the later stages of the experiment (introduction of Nalbuphine for 6 weeks), the pathological changes increased and manifested by destructuring the wall of the common bile duct, disorganization of cholangiocytes, thinning of the cell layer due to detachment of cholangiocytes, polymorphism of their nuclei, destruction of intercellular junctions, stratification of its own plate, vacuolar dystrophy of the muscular membrane “varicose” expansion of venules, significant smooth muscle hyperplasia of arterioles, the presence of perivascular lymphocytic infiltrates in the duct wall.

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“…1). BDL-induced liver fibrosis is accompanied by hepatocytes apoptosis which is an important feature of liver injury 22,23 . However, the number of apoptotic cells marked by TUNEL fluorescence staining in nonfibrotic regions of the fibrotic liver tissue was evidently decreased in following therapeutic treatment with roseotoxin B ( Fig.…”

Section: Roseotoxin B Therapeutically Improved Bile Duct Ligation (Bdmentioning

confidence: 99%

Roseotoxin B alleviates cholestatic liver fibrosis through inhibiting PDGF-B/PDGFR-β pathway in hepatic stellate cells

Wang

Gao

et al. 2020

Cell Death Dis

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Identifying effective anti-fibrotic therapies is a major clinical need that remains unmet. In the present study, roseotoxin B was shown to possess an improving effect on cholestatic liver fibrosis in bile duct-ligated mice, as proved by histochemical and immunohistochemical staining, hepatic biochemical parameters, and TUNEL apoptotic cell detection in tissue sections. Using cellular thermal shift assay, computational molecular docking, microscale thermophoresis technology, and surface plasmon resonance biosensor, we confirmed that PDGFR-β was a direct target of roseotoxin B in fibrotic livers. Of note, human tissue microarrays detected pathologically high expression of p-PDGFR-β in liver samples of~80% of patients with liver fibrosis and cirrhosis. PDGF-B/PDGFR-β pathway promotes transdifferentiation and excessive proliferation of hepatic stellate cells (HSCs), which is a very crucial driver for liver fibrosis. Meaningfully, roseotoxin B blocked the formation of PDGF-BB/PDGFR-ββ complex by targeting the D2 domain of PDGFR-β, thereby inhibiting the PDGF-B/PDGFR-β pathway in HSCs. In summary, our study provided roseotoxin B as a unique candidate agent for the treatment of liver fibrosis.

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Melatonin Alleviates Liver Apoptosis in Bile Duct Ligation Young Rats

Cited by 24 publications

References 42 publications

Neuropeptide Y1 Receptor Regulates Glucocorticoid-Induced Inhibition of Osteoblast Differentiation in Murine MC3T3-E1 Cells via ERK Signaling

Neuropeptide Y1 Receptor Regulates Glucocorticoid-Induced Inhibition of Osteoblast Differentiation in Murine MC3T3-E1 Cells via ERK Signaling

Morphological features of the wall of common bile duct under the conditions of experimental opioid exposure

Roseotoxin B alleviates cholestatic liver fibrosis through inhibiting PDGF-B/PDGFR-β pathway in hepatic stellate cells

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