• Title/Summary/Keyword: Mouse liver

Search Result 745, Processing Time 0.031 seconds

Ahnak depletion accelerates liver regeneration by modulating the TGF-β/Smad signaling pathway

  • Yang, Insook;Son, Yeri;Shin, Jae Hoon;Kim, Il Yong;Seong, Je Kyung
    • BMB Reports
    • /
    • v.55 no.8
    • /
    • pp.401-406
    • /
    • 2022
  • Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

Therapeutic effects of selective p300 histone acetyl-transferase inhibitor on liver fibrosis

  • Hyunsik Kim;Soo-Yeon Park;Soo Yeon Lee;Jae-Hwan Kwon;Seunghee Byun;Mi Jeong Kim;Sungryul Yu;Jung-Yoon Yoo;Ho-Geun Yoon
    • BMB Reports
    • /
    • v.56 no.2
    • /
    • pp.114-119
    • /
    • 2023
  • Liver fibrosis is caused by chronic liver damage and results in the aberrant accumulation of extracellular matrix during disease progression. Despite the identification of the HAT enzyme p300 as a major factor for liver fibrosis, the development of therapeutic agents targeting the regulation of p300 has not been reported. We validated a novel p300 inhibitor (A6) on the improvement of liver fibrosis using two mouse models, mice on a choline-deficient high-fat diet and thioacetamide-treated mice. We demonstrated that pathological hall-marks of liver fibrosis were significantly diminished by A6 treatment through Masson's trichrome and Sirius red staining on liver tissue and found that A6 treatment reduced the expression of matricellular protein genes. We further showed that A6 treatment improved liver fibrosis by reducing the stability of p300 protein via disruption of p300 binding to AKT. Our findings suggest that targeting p300 through the specific inhibitor A6 has potential as a major therapeutic avenue for treating liver fibrosis.

Cloning and Expression of Human Liver UDP-Glucuronosyltransferase cDNA, UDPGTh2

  • Dong, Misook;Owens, Ida-S.;Sheen, Yhun-Yhong
    • Archives of Pharmacal Research
    • /
    • v.20 no.5
    • /
    • pp.459-464
    • /
    • 1997
  • The human liver cDNA clone UDPGTh2, encoding a liver UDP-glucuronosyltransferase (UDPGT) was isolated from a .gamma. gt 11 cDNA library by hybridization to mouse transferase cDNA clone, UDPGTm1. UDPGTh2 encoded a 529 amino acid protein with an amino terminus membrane-insertion signal peptide and a carboxyl terminus membrane-spanning region. There were three potential asparagine-linked glycosylation sites at residues 67, 68, and 315. In order to obtain UDPGTh2 protein encoded from cloned human liver UDP-glucuronosyltransferase cDNA, the clone was inserted into the pSVL vector (pUDPGTh2) and expressed in COS 1 cells. The presence of a transferase with Mr-52,000 in transfected cells cultured in the presence of $[^{35}S]$ methionine was shown by immunocomplexed products with goat antimouse transferase IgG and protein A-Sepharose and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. The expressed UDPGT was a glycoprotein as indicated by electrophoretic mobility shift in Mr-3,000-4,000 when expressed in the presence of tunicamycin. The extent of glycosylation was difficult to assess, although one could assume that glycosyl structures incorporated at the level of endoplasmic reticulum were always the core oligosaccharides. Thus, it is likely that at least two moieties inserted can account for the shift of Mr-3,000-4,000. This study demonstrates the cDNA and deduced amino acid sequence of human liver UDP-glucuronosyltransferase cDNA, UDPGTh2.

  • PDF

Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis

  • Jang, Yu Jin;An, Su Yeon;Kim, Jong-Hoon
    • BMB Reports
    • /
    • v.50 no.2
    • /
    • pp.58-59
    • /
    • 2017
  • The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

THE SHELLFISH POISON IN TAPES PHILIPPINARUM LISCHKE (바지락독에 관한 연구)

  • CHUN Seh Kyu;KIM Seong Jun;CHANG Dong Suck
    • Korean Journal of Fisheries and Aquatic Sciences
    • /
    • v.2 no.2
    • /
    • pp.139-146
    • /
    • 1969
  • Incidents of poisoning caused by edible marine bivalve, Tapes philippinarum in Kojedo, Korea were reported in March 1968 and 1969. The results of the present investigation revealed that the incidents were caused by hemorrhagic diathesis and liver injuries, as those caused by acute yellow atrophic liver. The minimal lethal dose of the liver extract of the bivalve varied with seasons. The dose was 0.02ml in March and increased to 0.25ml in April-May 1969. After lune the extract showed no toxicity. Phthalein reaction of smashed liver solution of the bivalve showed a great variation with seasons. In March the values of $P_1$(crude solution) and $P_2$ (boiled one) were 0.1 and 10, at its strongest toxicity. In May those of $P_1\;and\;P_2$ were 1 and 1,000. However the mouse died after intraperitoneal administration of 0.25ml of the liver extract at the $P_2$ value of 1,000. For this reason, determination of the toxicity is difficult by judging from the phthalein reaction alone. The bivalves collected from Pusan, Kaduk, Koje, Hansan, Yeosu, Mokpo and Kunsan were found nontoxic during April-August 1969.

  • PDF

Studies on the Effectiveness of Ginseng Preparation (인삼(人蔘) 제제(製劑)의 효능(效能)에 관한 연구(硏究))

  • Han, Byung-Hoon;Park, Myung-Hwan;Shin, Sang-Chul
    • Korean Journal of Pharmacognosy
    • /
    • v.15 no.2
    • /
    • pp.98-103
    • /
    • 1984
  • A ginseng preparation consisting of ginseng ext., lycii fructus ext., four vitamins and caffeine was chosen and its efficacy was evaluated with respect to nutritional supplement, antifatigue activity and liver protective action. Animals administered orally in both one-third and three fold doses of the preparation showed no significant increments of their body weights when compared with those of the normal animals, suggesting no supplemental activity. However, the preparation in the above two doses significantly prolonged swimming time to 53 and 63%, respectively. Ginseng and lycii fructus ext. were found to be responsible for the antifatigue activity. And also the preparation significantly inhibited lipid peroxidation of mouse liver after ethanol-induced acute intoxication.

  • PDF

Effects of Hesperetin and Naringenin on Lipid Concentration in Orotic Acid Treated Mice (오르트산 투여 마우스의 지질농도에 미치는 Hesperetin 및 Naringenin의 영향)

  • 차재영;김석영;정순재;조영수
    • Journal of Life Science
    • /
    • v.9 no.4
    • /
    • pp.389-394
    • /
    • 1999
  • Male mice (ddY strain) were fed a laboratory chow diet containing 10% sucrose supplemented with orotic acid, hesperetin or naringenin at the 1% level for 14 days. the concentrations of liver triacylglycerol and cholesterol were significantly lower in the OA group than in the control group. When both flavonoids and orotic acid were administered simultaneously, the orotic acid-dependent decrease in liver triacylglycerol and cholesterol were attenuated slightly. The concentration of serum cholesterol in the orotic acid group or the control group was lower than in the orotic acid groups supplemented with hesperetin or naringenin. There were no significantly difference in body weight gain, diary food intake, and the serum concentrations of triacylglycerol and high-density-lipoprotein cholestrol. It was concluded that the inducement of fatty liver in mice failed to feeding a laboratory chow diet containing 10% sucrose supplemented with 1% orotic acid for 14 days.

  • PDF