| First Author | Yanda MK | Year | 2017 |
| Journal | Am J Physiol Renal Physiol | Volume | 313 |
| Issue | 4 | Pages | F997-F1004 |
| PubMed ID | 28747357 | Mgi Jnum | J:283230 |
| Mgi Id | MGI:6382323 | Doi | 10.1152/ajprenal.00186.2017 |
| Citation | Yanda MK, et al. (2017) An inhibitor of histone deacetylase 6 activity, ACY-1215, reduces cAMP and cyst growth in polycystic kidney disease. Am J Physiol Renal Physiol 313(4):F997-F1004 |
| abstractText | Adult-onset autosomal-dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene, leading to malfunction of their gene products, polycystin 1 or 2. Histone deacetylase 6 (HDAC6) expression and activity are increased in PKD1 mutant renal epithelial cells. Here we studied the effect of ACY-1215, a specific HDAC6 inhibitor, on cyst growth in ADPKD. Treatment with ACY-1215 slowed cyst growth in a mouse model of ADPKD that forms massive cysts within 3 wk after knockout of polycystin 1 function. It also prevented cyst formation in MDCK.2 cells, an in vitro model of cystogenesis, and in an ADPKD cell line derived from the proximal tubules from a pkd1(-/-.)mouse (PN cells). In PN cells ACY-1215 also reduced the size of already established cysts. We found that ACY-1215 lowered cAMP levels and protein expression of adenylyl cyclase 6. Our results suggest that HDAC6 could potentially serve as a therapeutic target in ADPKD. |
