Renal fibrosis is a hallmark of chronic kidney disease and contributes to the pathogenesis of terminal kidney disease. It has been observed that overexpression of aldosterone, a steroid hormone that regulates salt and water balance, is sufficient to induce renal fibrosis. Aldosterone is a mammalian hormone and is not normally found in Drosophila.
Aldosterone fed to adult flies over several weeks results in proteinuria and suppressed filtration by nephrocytes; elevated levels PRC (prc), an extracellular matrix protein, are observed around cardiac-nephrocyte tissue. Similar phenotypes are observed for adult flies fed ecdysone, but not for flies fed 20-hydroxyecdyone. These phenotypes appear to be effected via the DopEcR receptor, rather than the EcR, the canonical nuclear hormone ecdysone receptor. DopEcR s a dual G-protein-coupled receptor (GPCR) that can be activated by dopamine or by ecdysone. There are two genes in human (GPR21 and GPR52) orthologous to DopEcR.
[updated Oct. 2020 by FlyBase; FBrf0222196]
Chronic kidney disease results in the loss of renal cells and their replacement by extracellular matrix, independent of the associated disease (Nogueira et al., 2017; pubmed:280642150).
Aldosterone is a steroid hormone synthesized in the adrenal gland that acts a physiologic regulator of salt and water balance (https://www.sciencedirect.com/topics/neuroscience/aldosterone).
The renin-angiotensin-aldosterone system (RAAS) plays a key role in the progression of chronic kidney disease (CKD). Recently, blocking a class of aldosterone receptor has been shown to slow progression of CKD (Minakuchi, et al. 2020; pubmed:33024237).
Low-scoring ortholog of human GPR21 and GPR52; despite low scores, both are best hits and best reverse hits.
