Transcription profile of genes affected in response to pathological changes in drug-induced rat model of acute kidney injury.

ABSTRACT

OBJECTIVE: The objective of the present study was to examine the changes in the expression profile of certain genes in rat model of gentamicin-induced acute kidney injury (AKI) and to see whether time period and routes of administration affect their expression levels. METHODS: Rat AKI model was established with gentamicin injection using two different routes of administration and two different time periods. The models were evaluated through histopathological observations. Renal specific genes were selected on the basis of their role during kidney injury. These genes were analyzed through reverse transcriptase (RT) PCR. RESULTS: Marked disorganization of normal structure of proximal and distal tubules was observed in all the gentamicin-treated groups. Many tubules showed loss of brush border and presence of intratubular protein casts. Changes in gene expression levels were observed for kidney injury molecule (KIM-1), osteopontin, bone morphogenic protein-7 (BMP-7), extracellular signal-regulated kinases (ERK), stem cell factor (SCF) and IL-7 receptor with different levels of significance in the renal injury groups studied depending on the time period and route of administration. CONCLUSION: Gene expression seems to be dependent partly on the type of injury, route of administration and time period after induction of injury. An improved mechanistic understanding of gene regulation pathways in AKI may provide basis for potential therapeutic development.