Usage Information
Citation Information: JCI Insight. 2017;2(23):e97128. https://doi.org/10.1172/jci.insight.97128.
Abstract
Primary and secondary hypertension are major risk factors for cardiovascular disease, the leading cause of death worldwide. Elevated secretion of aldosterone resulting from primary aldosteronism (PA) is a key driver of secondary hypertension. Here, we report an unexpected role for the ubiquitin ligase Siah1 in adrenal gland development and PA. Siah1a–/– mice exhibit altered adrenal gland morphology, as reflected by a diminished X-zone, enlarged medulla, and dysregulated zonation of the glomerulosa as well as increased aldosterone levels and aldosterone target gene expression and reduced plasma potassium levels. Genes involved in catecholamine biosynthesis and cAMP signaling are upregulated in the adrenal glands of Siah1a–/– mice, while genes related to retinoic acid signaling and cholesterol biosynthesis are downregulated. Loss of Siah1 leads to increased expression of the Siah1 substrate PIAS1, an E3 SUMO protein ligase implicated in the suppression of LXR, a key regulator of cholesterol levels in the adrenal gland. In addition, SIAH1 sequence variants were identified in patients with PA; such variants impaired SIAH1 ubiquitin ligase activity, resulting in elevated PIAS1 expression. These data identify a role for the Siah1-PIAS1 axis in adrenal gland organization and function and point to possible therapeutic targets for hyperaldosteronism.
Authors
Marzia Scortegagna, Annabel Berthon, Nikolaos Settas, Andreas Giannakou, Guillermina Garcia, Jian-Liang Li, Brian James, Robert C. Liddington, José G. Vilches-Moure, Constantine A. Stratakis, Ze’ev A. Ronai
Usage data is cumulative from December 2017 through October 2018.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 1,015 | 0 |
| 269 | 0 | |
| Figure | 225 | 0 |
| Table | 68 | 0 |
| Supplemental data | 37 | 0 |
| Citation downloads | 24 | 0 |
| Totals | 1,638 | 0 |
| Total Views | 1,638 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
