A novel investigation on the role of specific microRNAs in podocytes and their influence in renal diseases

Iddo Z. Ben-Dov, M.D., Ph.D., Laboratory of Medical Transcriptomics, Hadassah Med. Ctr.

MicroRNAs (or miRNAs) comprise a novel class of small, non-coding endogenous RNAs that regulate gene expression of about half of human genes. They can therefore influence both normal and pathological conditions in diverse biological systems. Their discovery added a new dimension to the understanding of complex gene regulatory networks in humans and animals alike. For example, a successful clinical trial utilizing a miRNA therapeutic for suppression of hepatitis C virus replication have raised the possibility for developing miRNA-based therapeutics for other diseases as well. Since they play an important role in gene regulation, any mutations or production disturbance can cause disease in humans. Podocytes are specialized kidney cells responsible for the filtration of waste products. They cannot survive without their miRNAs. Several studies have uncovered the importance of miRNAs for podocyte development and function. Research carried out in mice indicated that a disturbed production of miRNAs in their podocytes developed severe kidney disease. Thus, there is great interest in the research community to evaluate the role of miRNAs in the kidney including their value as therapeutic targets for glomerular diseases. Indeed, the glomerulus is the essential functional unit for renal filtration of debris. However, little is known yet about the precise roles of specific miRNAs in the maintenance of podocyte structure and function.

Dr. Iddo Ben-Dov, Senior Physician in the Dept. of Nephrology, Laboratory of Medical Transcriptomics at Hadassah and his research team are undertaking an investigation to decipher the mechanism by which disruption of miRNA production causes kidney disease and to identify the specific miRNAs that are crucial for podocytes. They are searching to better understand the source of miRNA dependence to podocytes, which ones are implicated in this dependence and eventually to manipulate their function as therapeutic targets. Dr. Ben-Dov and research team have developed sophisticated high-throughput tools which are an advanced technology to screen quickly miRNAs. Armed with these advanced tools, they intend to reveal the role of specific miRNAs in maintaining podocyte viability and function which will contribute to our understanding of, and our ability to manipulate, glomerular disorders involving the kidneys.

The encouraging preliminary results and advanced technology used by Dr. Ben-Dov and his team could serve as a model to those researchers interested in miRNA research and in addition, could spark high interest in the development of modalities to block/manipulate specific miRNAs and their function in the kidney. This investigation represents an exciting avenue for new therapies for the prevention and treatment of various debilitating renal diseases.