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Mineralocorticoid receptors in non-alcoholic fatty liver disease
Barbara Schreier1, Alexander Zipprich2, Henriette Uhlenhaut3
1Julius-Bernstein-Institute of Physiology, Medical Faculty of the Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.
Abstract:
Liver diseases are the fourth common death in Europe responsible for about 2 million death per year worldwide. Among the known detrimental causes for liver dysfunction are virus infections, intoxications and obesity. The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor activated by aldosterone or glucocorticoids but also by pathological milieu factors. Canonical actions of the MR take place in epithelial cells of kidney, colon and sweat glands and contribute to sodium reabsorption, potassium secretion and extracellular volume homeostasis. The non-canonical functions can be initiated by inflammation or an altered micro-milieu leading to fibrosis, hypertrophy and remodelling in various tissues. This narrative review summarizes the evidence regarding the role of MR in portal hypertension, non-alcoholic fatty liver disease, liver fibrosis and cirrhosis, demonstrating that inhibition of the MR in vivo seems to be beneficial for liver function and not just for volume regulation. Unfortunately, the underlying molecular mechanisms are still not completely understood. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
Insights
Mineralocorticoid receptor (MR) inhibition shows promise for improving liver function in various liver diseases, including non-alcoholic fatty liver disease and cirrhosis. Further research is needed to fully understand the molecular mechanisms behind these beneficial effects.
Area of Science:
- Hepatology
- Endocrinology
- Molecular Biology
Background:
- Liver diseases cause significant global mortality, with viral infections, obesity, and intoxications as key contributors.
- The mineralocorticoid receptor (MR) is a nuclear receptor activated by aldosterone and glucocorticoids, playing roles in homeostasis and disease.
- Non-canonical MR functions are implicated in inflammation, fibrosis, and tissue remodeling.
Purpose of the Study:
- To review the evidence on the role of MR in liver diseases.
- To evaluate the therapeutic potential of MR inhibition in liver conditions.
Main Methods:
- Narrative review of existing literature.
- Analysis of studies investigating MR's role in portal hypertension, NAFLD, fibrosis, and cirrhosis.
Main Results:
- MR inhibition in vivo appears beneficial for liver function beyond its known effects on volume regulation.
- Evidence suggests MR plays a role in the pathogenesis of non-alcoholic fatty liver disease, fibrosis, and cirrhosis.
Conclusions:
- Targeting the mineralocorticoid receptor may offer a novel therapeutic strategy for managing liver diseases.
- The precise molecular mechanisms underlying MR's impact on liver pathology require further elucidation.
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