Exposure of proximal tubule cells to fluid shear stress alters transcription of metabolic pathway enzymes

Abstract

Cells lining the proximal tubule (PT) of the kidney are specialized for efficient recovery of ions, glucose, and proteins from the glomerular filtrate. Despite their high glucose levels, PT cells in vivo utilize gluconeogenic rather than glycolytic pathways to maintain the robust metabolic activity needed to carry out their functions. In contrast, the reliance of PT cell cultures on glycolytic metabolism has been a significant limitation in studying the regulation of PT function in vitro. We discovered recently that opossum kidney (OK) cells cultured under continuous fluid shear stress (FSS) develop morphological and functional characteristics that more closely resemble PT cells in vivo compared with cells cultured under static conditions. We performed RNA Seq on OK cells maintained under static conditions or exposed to FSS for up to 96 h. Principal component analysis confirmed significant time‐ and FSS‐dependent changes in gene expression. Consistent with enzyme activity profiles described in the PT, we observed an increase in transcripts encoding enzymes in the gluconeogenic pathway in OK cells cultured under FSS, and a concomitant reduction of transcripts encoding glycolytic enzymes. Current studies are underway to extend and validate our observations using complementary approaches. Our data provide further support that OK cell culture under FSS provides an improved model of the PT.Support or Funding InformationTsinghua MD Scholars ProgramNIH R01 DK101484This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.