Protective Mechanism of MIF Inhibitor ISO-1 on Intrahepatic Bile Duct Cells in Rats with Severe Acute Pancreatitis

Tet is a type of alkaloid extracted fromStephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP). The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

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Placental Chorionic Plate-derived Mesenchymal Stem Cells Ameliorate Severe Acute Pancreatitis by Regulating Macrophages Polarization via Secreting TSG-6

10.21203/rs.3.rs-167350/v1 ◽

2021 ◽

Author(s):

Qilin Huang ◽

Xiumei Cheng ◽

Chen Luo ◽

Shuxu Yang ◽

Shuai Li ◽

...

Keyword(s):

Stem Cells ◽

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Systemic Inflammation ◽

Therapeutic Efficacy ◽

Pancreatic Injury ◽

Protective Mechanism ◽

M2 Polarization ◽

Injured Tissue ◽

Chorionic Plate

Abstract BackgroundMesenchymal stem cells (MSCs) hold promising potential to treat systemic inflammatory diseases including severe acute pancreatitis (SAP). In our previous study, placental chorionic plate-derived MSCs (CP-MSCs) were found to possess superior immunoregulatory capability. However, the therapeutic efficacy of CP-MSCs on SAP and their underlying mechanism remain unclear.MethodsThe survival and colonization of exogenous CP-MSCs were observed by bioluminescence imaging and CM-Dil labeling in rodent animal models of SAP. The therapeutic efficacy of CP-MSCs on SAP rats was evaluated by pathology scores, the levels of pancreatitis biomarkers as well as the levels of inflammatory factors in pancreas and serum. The potential protective mechanism of CP-MSCs in SAP rats was explored by selectively depleting M1 or M2 phenotype macrophages and knocking down the expression of TSG-6.ResultsExogenous CP-MSCs could survive and colonize in the injured tissue of SAP such as lung, pancreas, intestine and liver. Meanwhile, we found that CP-MSCs alleviated pancreatic injury and systemic inflammation by inducing macrophages to polarize from M1 to M2 in SAP rats. Furthermore, our data suggested that CP-MSCs induced M2 polarization of macrophages by secreting TSG-6, and TSG-6 played a vital role in alleviating pancreatic injury and systemic inflammation in SAP rats. Notably, we found that a high inflammation environment could stimulate CP-MSCs to secrete TSG-6.ConclusionExogenous CP-MSCs tended to colonize in the injured tissue, and reduced pancreatic injury and systemic inflammation in SAP rats through inducing M2 polarization of macrophages by secreting TSG-6. Our study provides a new treatment strategy for SAP, and initially explains the potential protective mechanism of CP-MSCs on SAP rats.

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Selective and organotypic culture of intrahepatic bile duct cells from adult pig liver

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-998-0033-x ◽

1998 ◽

Vol 34 (10) ◽

pp. 785-798 ◽

Cited By ~ 14

Author(s):

Neil C. Talbot ◽

Thomas J. Caperna

Keyword(s):

Bile Duct ◽

Organotypic Culture ◽

Intrahepatic Bile Duct ◽

Pig Liver ◽

Duct Cells

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Resveratrol Suppresses Severe Acute Pancreatitis-Induced Microcirculation Disturbance through Targeting SIRT1-FOXO1 Axis

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/8891544 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Yuping Rong ◽

Jun Ren ◽

Wei Song ◽

Renshen Xiang ◽

Yuhang Ge ◽

...

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Mrna Level ◽

Dry Weight ◽

Underlying Mechanism ◽

Vital Role ◽

Protective Mechanism ◽

Ang Ii ◽

Microcirculation Disturbance ◽

Microcirculatory Function

Background. Resveratrol (RSV), one of the SIRT1 agonists, has the ability of alleviating severe acute pancreatitis (SAP); however, the concrete protective mechanism remains unknown. It is noteworthy that microcirculation disturbance plays a vital role in SAP, and the SIRT1/FOX1 axis can regulate microcirculation. Therefore, this study is aimed at ascertaining what is the underlying mechanism of the protective effect of RSV on SAP, and whether it is associated with alleviating microcirculation disturbance by regulating the SIRT1/FOX1 axis. Method. The model of SAP was induced by retrograde injection of sodium taurodeoxycholate into the bile duct of the rats. The pancreatic wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α ratios; microcirculatory function; and SIRT1 activity were examined. ELISA was used to examine the serum level of lipase, amylase, hemorheology, ET, NO, TXB2, and 6-keto-PGF1α and the content of SIRT1, VEGF, Ang I, and Ang II in the pancreas. RT-PCR was used to examine the mRNA level of VEGF, Ang I, and Ang II. Western blotting was used to detect SIRT1, FOXO1, and acetyl-FOXO1. Immunoprecipitation was used to examine the interaction of SIRT1 and FOXO1. Results. Resveratrol can significantly decrease the expression of lipase, amylase, acetyl-FOXO1, VEGF, Ang II, ET, NO, TXB2, and 6-keto-PGF1α and the ratio of wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α by improving microcirculatory dysfunction and blood viscosity in SAP. Moreover, resveratrol can also promote the interaction of SIRT1 and FOXO1 and increase SIRT1 activity and the expression of SIRT1 and Ang I. The SIRT1 inhibitor, Sirtinol (EX527), obliviously reversed the effects of RSV on SAP. Conclusion. Resveratrol can protect rats against SAP, and its protective mechanism is associated with suppressing microcirculation disturbance through activating SIRT1-FOXO1 axis.

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The origin of intrahepatic bile duct cells in the mouse

Development ◽

10.1242/dev.79.1.25 ◽

1984 ◽

Vol 79 (1) ◽

pp. 25-39

Author(s):

Nobuyoshi Shiojiri

Keyword(s):

Bile Duct ◽

Mouse Liver ◽

Intrahepatic Bile Duct ◽

Normal Liver ◽

Liver Parenchyma ◽

Newborn Mice ◽

Embryonic Mouse ◽

Intrahepatic Bile Ducts ◽

Duct Cells ◽

Liver Fragments

The origin of the intrahepatic bile ducts in the embryonic mouse liver was investigated. At 12·5 and 13·5 gestation days in the C3H/Tw strain mouse, the liver parenchyma contains morphologically and histochemically homogeneous immature hepatocytes but not bile duct cells. When the liver fragments were cultured in the testis, immature hepatocytes differentiated into large hepatocytes for the most part and also into bile duct cells. In contrast, when the similar liver fragments were cultured under the skin of newborn mice, bile duct cells differentiated much earlier in all transplants than those cultured in the testis. These bile duct cells were considered to be the intrahepatic bile duct cells, since they did not form biliary glands but possessed a basal lamina and histochemical characteristics of intrahepatic bile duct cells of the normal liver. The origin of the endodermal epithelial cells in the mouse liver is discussed with special attention to the differentiation of the intrahepatic bile duct cells from the immature hepatocytes.

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