ArticleHypertension (Dallas, Tex. : 1979)2024
Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.
Article in Hypertension (Dallas, Tex. : 1979), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Renin cells orchestrate a neuro-endocrine microenvironment of the kidney arterial tree in health and disease.JCI insight · 2026Article
- The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl-4-hydroxylases 2 and 3.The Journal of physiology · 2026Article
- Krüppel-like factor 2 regulates renin expression in mature juxtaglomerular cells.American journal of physiology. Renal physiology · 2026Article
- Balancing Blood Pressure Targets and Kidney Health: The Potential Risk of Kidney Disease Due to Concentric Arterial and Arteriolar Hypertrophy From Renin-Angiotensin-Aldosterone Inhibitors.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Piezo channels in JG cells do not regulate renin expression or renin release to the circulation.Clinical science (London, England : 1979) · 2024Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundRenin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear.
methodsWe treated As4.1 cells (tumoral cells derived from mouse juxtaglomerular cells that constitutively express renin) with 3 inhibitors that target different factors required for renin transcription: H-89-dihydrochloride, PKA (protein kinase A) inhibitor; JQ1, Brd4 bromodomain inhibitor; and A-485, p300/CBP inhibitor. We performed assay for transposase-accessible chromatin with sequencing (ATAC-seq), single-cell RNA sequencing, cleavage under targets and tagmentation (CUT&Tag), and chromatin immunoprecipitation sequencing for H3K27ac (acetylation of lysine 27 of the histone H3 protein) and p300 binding on biological replicates of treated and control As4.1 cells.
resultsIn response to each inhibitor,
conclusionsInhibition of renin expression in cells that constitutively synthesize and release renin is regulated by an epigenetic switch from an active to poised state associated with decreased cell-cell communication and an epithelial-mesenchymal transition. This work highlights and helps define the factors necessary for renin cells to alternate between myoendocrine and contractile phenotypes.
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