News From The Journal Of Clinical Investigation: Oct. 23, 2008

Main Category: Liver Disease / Hepatitis
Also Included In: Biology / Biochemistry;  Immune System / Vaccines;  Allergy
Article Date: 24 Oct 2008 - 5:00 PDT


HEPATOLOGY: A new regulator in the liver: miR15a controls the development of cysts

Polycystic liver and kidney diseases are a family of disorders that are characterized by a range of symptoms. For example, individuals with ADPKD have multiple cysts in both their liver and their kidneys, whereas individuals with ARPKD usually only have cysts in their kidneys (although cysts can develop in the liver later in life) and individuals with ADPLD only have cysts in their liver. Nicholas LaRusso and colleagues, at the Mayo Clinic College of Medicine, Rochester, have now provided new insight into the molecular mechanisms underlying the development of cysts (cystogenesis) in these diseases through their analysis of patient tissue and a rat model of polycystic kidney disease.

The authors analyzed changes in the expression of recently identified regulatory RNA molecules known as microRNAs (miRNAs) in a cell line generated from bile duct cells known as cholangiocytes from PKC rats, a model of ARPKD. One specific miRNA caught their eye, miR15a, as its expression was substantially decreased in these cells compared with cholangiocytes from normal rats. A similar decrease in miR15a levels was then observed in liver tissue from PCK rats as well as liver tissue from patients with either ADPKD or ARPKD. Decreased miR15a expression was associated with increased amounts of Cdc25a, a protein that promotes cell proliferation. Additional analysis of the effects of artificially increasing and decreasing the expression of miR15a in cholangiocytes from PKC rats and normal rats, respectively, led the authors to conclude that suppression of miR15a contributes to the development of cysts in the liver through dysregulation of Cdc25A.

In an accompanying commentary, Andrew Chu and Joshua R. Friedman, at the University of Pennsylvania School of Medicine, Philadelphia, discuss the importance of this work and the questions that it leads us to ask.

TITLE: MicroRNA15a modulates expression of the cell-cycle regulator Cdc25A and affects hepatic cystogenesis in a rat model of polycystic kidney disease

AUTHOR CONTACT:
Nicholas LaRusso
Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=34922

ACCOMPANYING COMMENTARY
TITLE: A role for microRNA in cystic liver and kidney diseases

AUTHOR CONTACT:
Joshua R. Friedman
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36870

IMMUNOLOGY: Tracking down the human equivalent of the mouse protein mFc-gamma-RIV

A recently identified mouse protein mFc-gamma-RIV, so called because it binds IgG2a and IgG2b, was thought to be equivalent to the human protein hFc-gamma-RIIIA. However, Pierre Bruhns and colleagues, at the Institut Pasteur, France, have now found that mFc-gamma-RIV is, in fact, equivalent to the human protein hFc-epsilon-R1(alpha, gamma).

In the study, mFc-gamma-RIV was found to bind proteins known as IgE molecules, while hFc-gamma-RIIIA did not. Furthermore, mFc-gamma-RIV binding to IgE had functional consequences. First, in vitro, when mFc-gamma-RIV on immune cells known as macrophages bound IgE immune complexes, the cells were induced to secrete cellular factors known as cytokines. Second, when mice were engineered to express no proteins that bind IgG and IgE molecules except mFc-gamma-RIV, the mice still developed IgE-induced lung inflammation (a model of asthma). As hFc-epsilon-R1(alpha, gamma) is expressed on macrophages and neutrophils, in particular in individuals who are allergic, the authors suggest that mFc-gamma-RIV is equivalent to hFc-epsilon-R1(alpha, gamma) and that their analysis of this mouse protein provides insight into cellular interactions that might be important in individuals with allergic asthma.

TITLE: Fc-gamma-RIV is a mouse IgE receptor that resembles macrophage Fc-epsilon-RI in humans and promotes IgE-induced lung inflammation

AUTHOR CONTACT:
Pierre Bruhns
Institut Pasteur, Paris, France.

View the PDF of this article at: https://www.the-jci.org/article.php?id=36452

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Source: Karen Honey
Journal of Clinical Investigation

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