{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:48:00Z","timestamp":1790974080993,"version":"4.1.0"},"reference-count":59,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4,1]]},"abstract":"<jats:p>Polycystin 1 and polycystin 2 are large transmembrane proteins, which, when mutated, cause autosomal dominant polycystic kidney disease (ADPKD), a highly prevalent human genetic disease. The polycystins are thought to form a receptor-calcium channel complex in the plasma membrane of renal epithelial cells and elicit a calcium influx in response to mechanical stimulation, such as fluid flow across the apical surface of renal epithelial cells. The functional role of the polycystins in mechanosensation remains largely unknown. Here, we found that myocyte enhancer factor 2C (MEF2C) and histone deacetylase 5 (HDAC5), two key regulators of cardiac hypertrophy, are targets of polycystin-dependent fluid stress sensing in renal epithelial cells in mice. We show that fluid flow stimulation of polarized epithelial monolayers induced phosphorylation and nuclear export of HDAC5, which are crucial events in the activation of MEF2C-based transcription. Kidney-specific knockout of Mef2c, or genetrap-inactivation of a MEF2C transcriptional target, MIM, resulted in extensive renal tubule dilation and cysts, whereas Hdac5 heterozygosity or treatment with TSA, an HDAC inhibitor, reduced cyst formation in Pkd2\u2212\/\u2212 mouse embryos. These findings suggest a common signaling motif between myocardial hypertrophy and maintenance of renal epithelial architecture, and a potential therapeutic approach to treat ADPKD.<\/jats:p>","DOI":"10.1242\/dev.049437","type":"journal-article","created":{"date-parts":[[2010,2,25]],"date-time":"2010-02-25T04:40:59Z","timestamp":1267072859000},"page":"1075-1084","source":"Crossref","is-referenced-by-count":81,"title":["Polycystin-dependent fluid flow sensing targets histone deacetylase 5 to prevent the development of renal cysts"],"prefix":"10.1242","volume":"137","author":[{"given":"Sheng","family":"Xia","sequence":"first","affiliation":[{"name":"The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Li","sequence":"additional","affiliation":[{"name":"The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teri","family":"Johnson","sequence":"additional","affiliation":[{"name":"The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Seidel","sequence":"additional","affiliation":[{"name":"The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[{"name":"The Kidney Institute, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"The Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA"},{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042606501415200_R1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1126\/science.1099402","article-title":"Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus","volume":"305","author":"Azzam","year":"2004","journal-title":"Science"},{"key":"2021042606501415200_R2","doi-asserted-by":"crossref","first-page":"2819","DOI":"10.1093\/hmg\/ddn180","article-title":"Loss of polycystin-1 causes centrosome amplification and genomic instability","volume":"17","author":"Battini","year":"2008","journal-title":"Hum. 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