The role of ERp29/FOS/EMT pathway in excessive apoptosis of placental trophoblast cells in intrahepatic cholestasis of pregnancy.

BACKGROUND: Abnormal bile acid metabolism leading to changes in placental function during pregnancy. To determine whether endoplasmic reticulum protein 29 (ERp29) can mediate the pregnancy effects of cholestasis by altering the level of trophoblast cell apoptosis. METHODS: ERp29 in serum of 66 intrahepatic cholestasis of pregnancy (ICP) pregnant women and 74 healthy were detected by ELISA. Subcutaneous injection of ethinyl estradiol (E2) was used to induce ICP in pregnant rats. Taurocholic acid (TCA) was used to simulate the ICP environment, and TGF-ß1 was added to induce the epithelial mesenchymal transformation (EMT) process. The scratch, migration, and invasion test were used to detect the EMT process. ERp29 overexpression/knockdown vector were constructed and transfected to verify the role of ERp29 in the EMT process. Downstream gene was obtained through RNA-seq. RESULTS: Compared with the healthy pregnant women, the expression levels of ERp29 in serum of ICP pregnancy women were significantly increased (P < 0.001). ERp29 in the placenta tissue of the ICP pregnant rats increased significantly, and the level of apoptosis increased. The placental tissues of the ICP had high expression of E-cadherin and low expression of N-cadherin, snail1, vimentin. After HTR-8/SVneo cells were induced by TCA, EMT was inhibited, while the ERp29 increased. Cell and animal experiments showed that, knockdown of ERp29 reduced the inhibition of EMT, the ICP progress was alleviated. Overexpression of FOS salvaged the inhibitory effects of ERp29 on cell EMT. DISCUSSION: The high level of ERp29 in placental trophoblast cells reduced FOS mRNA levels, inhibited the EMT process and aggravated the occurrence and development of ICP.

Protective effect of a protein-free diet in acute experimental pancreatitis

1. Surgical time, amylase activiry and pancreatic protein, DNA and RNA content were measured in 38 control rats and in 104 rats injected with sodium taurocholate to induced acute pancreatitis after 21 days on one of four diets differing in protein, lipid and carbohidrate cocnent. 2. All of the parameters measured were lower in rats with pancreatitis than in controls maintained on thes same diets. Among the rats with pancreatitis, those reciving a protein-free survived longer and had significantly higher DNA, lower amylase activity and lower RNA and protein levels than those reciving a balanced diet or one that was high in protein or lipid content. 3. We conclude that acute pancratitis in rats has a more benign course in protein-undernourished animals

Early changes in bile secretion following relief of short-term biliary obstruction in the rat

Se estudiaron los efectos que produce una obstrucción biliar extrahepática de 2 h en la rata después de liberada la interrupción del flujo biliar (FB). Las actividades plasmáticas de fosfatasa alcalina y 5'-nucleotidasa aumentaron luego de la obstrucción. El aumento de la coleresis post-obstructiva fue debido a la mayor excreción biliar de ácidos biliares acumulados durante la obstrucción, la cual no fue acompañada por otros lípidos, como ocurre en ratas normales. La inyección en bolo de taurocolato de sodio (TC) puso de manifiesto una capacidad disminuida pra ser secretado en bilis y además, una disminución de la eficiencia colerética. A su vez, las ratas post-colestásicas mostraron una gran susceptibilidad al efecto inhibitorio del TC sobre el FB independiente de sales biliares. Dichas alteraciones podrían reflejar importantes daños en la membrana ocasionados por la salbiliar excretada, a pesar del corto período de la obstrucción, así como que las alteraciones observadas del FB dependiente e independiente de sales biliares pueden ser atribuidas a una incapacidad para reparar membranas en las ratas post-colestásicas

Efeito protetor da reduçäo do conteúdo enzimático do pâncreas na lesäo pulmonar da pancreatite aguda / Protective effect of reduction of pancreatic enzyme content on the pancreas in acute pulmonary pancreatitis

A lesao pulmonar surge em até 50-70 por cento dos pacientes com pancreatite aguda. A infusao de ceruleína em doses fisiológicas reduz o conteúdo enzimático do pâncreas com diminuiçao da taxa de mortalidade da pancreatite. Com objetivo de avaliar o efeito da reduçao do conteúdo enzimático do pâncreas sobre a lesao pulmonar da pancreatite aguda, foi induzida pancreatite em ratos Wistar através da infusao, dentro do ducto biliar, de soluçao de taurocolato de sódio a 5 por cento: grupo I, ratos com pancreatite; grupo II, ratos nos quais pancreatite foi induzida somente após reduçao do conteúdo enzimático do pâncreas, e grupo III, controle. A lesao pulmonar foi avaliada através da utilizaçao do corante azul de Evans, sendo menor no grupo II comparativamente ao I (P O,05). Especula-se que a reduçao do conteúdo enzimático do pâncreas diminui a lesao pulmonar da pancreatite aguda pela reduçao da quantidade de enzimas que atinge a circulaçao sistêmica.