Adenovirus‐mediated human aquaporin‐1 expression in hepatocytes improves lipopolysaccharide‐induced cholestasis

Marrone, Julieta; Danielli, Mauro; Gaspari, César I.; Marinelli, Raúl A.

doi:10.1002/iub.1689

Cited by 14 publications

(11 citation statements)

References 28 publications

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“…It is possible that even an excessive increase in body weight, as was the case for our proband, can increment the predisposition to cholestasis. As to intermittent cholestasis associated to ATP8B1, bacterial endotoxins such as lipopolysaccharides released from sites of infection [20] might induce the failure of bile transport, thus explaining intermittent cholestasis. Therefore, drugs that act on the transport of bile salts may prevent the occurrence of these conditions.…”

Section: Discussionmentioning

confidence: 99%

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Provenzano

Farina²,

Seidenari³

et al. 2021

Diagnostics

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Liver disease in pregnancy may present as an acute condition related to the gestational period, characterized by pruritus, jaundice, and abnormal liver function. The disease may be misdiagnosed with other liver diseases, some of which may have consequences for fetal health. It is therefore advisable to implement rapid diagnostic strategies to provide information for the management of pregnancy in these conditions. We report the case of a healthy woman with a twin pregnancy from homologous in vitro fertilization (IVF), who in the third trimester presented jaundice and malaise. Biochemical investigations and liver hyperechogenicity raised the suspicion of acute fatty liver disease of pregnancy (AFLP). Non-invasive prenatal whole-exome sequencing (WES) in the trio identified the Phe305Ile heterozygous variant in the ATP8B1 gene. Considering the twin pregnancy, the percentage of the variant versus the wild allele was of 31%, suggesting heterozygosity present in the mother alone. This analysis showed that the mother was affected by benign recurrent intrahepatic cholestasis of pregnancy (ICP1: # 147480) and indicated the opportunity to anticipate childbirth to avoid worsening of the mother’s health. WES after the birth of the twins confirmed the molecular data.

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Section: Discussionmentioning

confidence: 99%

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Provenzano

Farina²,

Seidenari³

et al. 2021

Diagnostics

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“…In contrast, some reports have shown that AQP1 induction decreases in ammation and apoptosis in hepatic and pulmonary injuries. Hepatocyte-induced AQP1 using adenovirus improves estrogen-induced and lipopolysaccharide-induced cholestasis in rats (31)(32)(33). Alpinetin, a Chinese medicine, alleviates lung AQP1 levels (34).…”

Section: Discussionmentioning

confidence: 99%

Exacerbation of hepatic damage in endothelial aquaporin 1 transgenic mice after experimental heatstroke.

Ohtaki¹,

Miyamoto²,

Suzuki³

et al. 2021

Preprint

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Background: Heatstroke is a life-threatening disease that causes body fluid loss and electrolyte abnormalities due to exposure to high ambient temperature (AT) and relative humidity (RH). Recently, global warming has increased the number of heatstroke patients worldwide. Aquaporin 1 (AQP1) is a water-selective protein that plays an important role in water homeostasis. However, the role of AQP1 in heatstroke has not been elucidated yet. Therefore, in this study, we examined the role of endothelial AQP1 using Tie2-Cre/LNL-AQP1 double transgenic (dTG) mice with an upregulation of aqp1 on endothelial cells. Methods: Tie2-Cre/LNL-AQP1 dTG mice were generated by breeding CAG-LNL(STOP)-AQP1 Tg and Tie2-Cre Tg mice. The transgenes were evaluated in the brain because brain vessels do not express aqp1. For production of experimental heatstroke, the mice were kept in a heatstroke chamber that was pre-heated at 41 °C AT and >99% RH for 1 h, and the blood, brain, kidney, and liver were collected 24 h later. Blood samples were analyzed for biochemical parameters such as electrolytes and tissue damage markers, and the organs were examined via morphological and immunohistological (3-nitrotyrosine (3-NT), AQP1, and Iba-1) staining. Results: Although no difference was observed in aqp1 expression in the whole brain, aqp1 was detected only in Tie2-Cre/LNL-AQP1 dTG mice after capillary deprivation. Moreover, AQP1 immunostaining also revealed immunoreaction in blood vessels. After heat exposure, electrolyte abnormalities were observed in both the wild and Tie2-Cre/LNL-AQP1 dTG mice compared to non-heat stroke wild mice. Hepatic damage markers, aspartate aminotransferase and alanine aminotransferase, were increased, and serum lactate dehydrogenase levels were significantly higher in Tie2-Cre/LNL-AQP1 dTG mice than in wild mice. Hematoxylin-eosin staining and 3-NT immunoreactivity in the liver also supported hepatic damage. Moreover, the number of hepatic vasculature adherent Iba-1 positive cells was significantly higher in Tie2-Cre/LNL-AQP1 dTG mice than in wild mice. Conclusions: In the present study, for the first time, we suggested that endothelial AQP1 contributes to hepatic damage after heatstroke.

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“…SL decreases plasma membrane fluidity, as a result of an increase in cholesterol and a decrease in phospholipids [46]. On the other hand, LPS treatment decreases cholesterol content in the canalicular membrane [47], an effect that could have been counteracted by SL co-treatment. SL effect would enable the stabilization of the transporters in lipid raft microdomains, thus preventing their transfer to non-raft structures, and their further endocytosis via a clathrin-dependent mechanism [48].…”

Section: Discussionmentioning

confidence: 99%

Spironolactone ameliorates lipopolysaccharide-induced cholestasis in rats by improving Mrp2 function: Role of transcriptional and post-transcriptional mechanisms

et al. 2020

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show abstract

Adenovirus‐mediated human aquaporin‐1 expression in hepatocytes improves lipopolysaccharide‐induced cholestasis

Cited by 14 publications

References 28 publications

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Prenatal Noninvasive Trio-WES in a Case of Pregnancy-Related Liver Disorder

Exacerbation of hepatic damage in endothelial aquaporin 1 transgenic mice after experimental heatstroke.

Spironolactone ameliorates lipopolysaccharide-induced cholestasis in rats by improving Mrp2 function: Role of transcriptional and post-transcriptional mechanisms

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