MicroRNAs as modulators of aquaporins

Abstract

The importance of aquaporins in normal as well as pathophysiological conditions has been well established by various studies. Yet these reports also highlight the lack and the need of natural regulators that could modulate the aquaporin expression. This study attempts to identify natural modulators for aquaporins and focuses on the widely prevalent endogenous cellular modulators, microRNAs. The entire aquaporin family consists of thirteen members classified into two major catergories as classical aquaporins and aquaglyceroporins. The initial study explored for possible microRNA regulators for the three commonly studied aquaporins, namely aquaporins 1, 2 and 4. Using one of the microRNAs that were identified, the study was extended into an in vivo animal model. Particular interest was on aquaporins 1 and 4 as they were highly implicated in brain associated pathologies. A relatively new phenomenon of transcriptional modulation by microRNAs was also explored in this study. As two different isoforms of aquaporin 4 were identified in the brain, the study investigated the potential to regulate the transcription of the longer aquaporin 4 isoform that is considered important in cerebral ischemia. Finally an attempt to identify a microRNA based regulator for aquaglyceroporin 9 was made for it is also expressed in the brain and considered to be crucial for energy metabolism. Thus the use of microRNAs as modulators for aquaporins 1, 2, 4, and 9 were explored in this thesis with emphasis on brain aquaporins 1, 4 and 9. This study provides evidence of possible microRNAs that could be used to regulate the expression of these selected aquaporins.