MicroRNA-21 aggravates cyst growth in a model of polycystic kidney disease

Ronak Lakhia, Sachin Hajarnis, Darren Williams, Karam Aboudehen, Matanel Yheskel, Chao Xing, Mark E. Hatley, Vicente E. Torres, Darren P. Wallace, Vishal Patel

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Autosomal dominant polycystic kidney disease (ADPKD), one of the most common monogenetic disorders, is characterized by kidney failure caused by bilateral renal cyst growth. MicroRNAs (miRs) have been implicated innumerous diseases, but the role of the senoncoding RNAs in ADPKD pathogenesis is still poorly defined. Here, we investigated the role of miR-21, an oncogenic miR, in kidney cyst growth. We found that transcriptional activation of miR-21 is a common feature of murine PKD. Furthermore, compared with renal tubules from kidney samples of normal controls, cysts in kidney samples from patients with ADPKD had increased levels of miR-21. cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and promoted miR-21 expression in cystic kidneys of mice. Genetic deletion of miR-21 attenuated cyst burden, reduced kidney injury, and improved survival of an orthologous model of ADPKD. RNA sequencing analysis and additional in vivo assays showed that miR-21 inhibits apoptosis of cyst epithelial cells, likelythrough direct repressionofits target geneprogrammed cell death 4. Thus, miR-21 functions downstream of the cAMP pathway and promotes disease progression in experimental PKD. Our results suggest that inhibiting miR-21 is a potential new therapeutic approach to slow cyst growth in PKD.

Original languageEnglish (US)
Pages (from-to)2319-2330
Number of pages12
JournalJournal of the American Society of Nephrology
Issue number8
StatePublished - 2016

ASJC Scopus subject areas

  • Nephrology


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