Endogenous factors and mechanisms of renoprotection and renal repair

An imbalance between renal damaging molecules and nephroprotective factors contributes to the development and progression of kidney diseases. Molecules with renoprotective properties might serve as biomarkers, drug targets as well as therapeutic options themselves.

For this review, we generated a set of renoprotective factors based on GeneRIF (Gene Reference Into Function) information available at NCBI's PubMed. The final set of manually curated renoprotective factors was investigated with respect to tissue-specific expression, subcellular location distribution and involvement in biological processes using information from gene ontology as well as information from protein-protein interaction databases. We furthermore investigated the factors in the context of clinical trials of renal disease and diabetes.

One hundred and ninety-three factors could be retrieved from the set of GeneRIFs on nephroprotection and renal repair. A large number of factors were either secretory molecules or plasma membrane receptors. Next to the elevated expression in renal tissue, also higher expression in connective tissue and pancreas was observed. The proteins could be assigned to the broad functional categories of cell proliferation and signalling, inflammatory response, apoptosis, blood pressure regulation as well as cellular response to different kinds of insults such as hypoxia, heat or mechanical stimulus. Eight factors are studied in clinical trials with additional ones being targeted by compounds.

We have generated a set of renoprotective factors based on the literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials.