647.7 - Changes in the Non-Coding Transcriptome of Short-Term Glucose-Challenged Human Glomerular Epithelial Cells May Give Insights into Early Molecular Events of Diabetic Kidney Disease

Nik Tsotakos (Penn State Harrisburg), Ryan Castaneira (Penn State Harrisburg), Josie Rice (Penn State Harrisburg), Savannah Kreiser (Penn State Harrisburg), Daniel Morris (Penn State Harrisburg)

Diabetic kidney disease is a complication of diabetes that takes years, sometimes decades, to develop. Our previous work on a podocyte-like cell line showed that phenotypic changes following exposure to high glucose, such as downregulation of podocalyxin and nephrin, are gradual and reversible. We also identified changes in the expression of long non-coding RNAs (lncRNA) MEG3, MEG8, and H19 in human glomerular epithelial cells (HGEC) chronically cultured in high glucose levels. In the present study, we aim to identify lncRNA that are dysregulated shortly after exposure of cells to high glucose and the cellular events that are associated with such dysregulation. Through a qPCR array, we identified approximately 20 upregulated and 20 downregulated lncRNA in HGEC that were exposed to high glucose for 2 weeks. These changes precede the terminal loss of podocyte markers and may provide insights to novel biomarkers for early-stage diabetic nephropathy. Additionally, ectopic expression of MEG3, a lncRNA upregulated in HGEC chronically treated with high glucose, modulates autophagy by inducing changes in p62/SQSTM1 protein levels.

Support or Funding Information

Supported by Penn State Harrisburg SSET. JR is supported by a Pennsylvania Academy of Sciences Student Research Grant and a Penn State University Erickson grant.