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RTN1 mediates progression of kidney disease by inducing ER stress

Ying Fan1,2, Wenzhen Xiao1,2, Zhengzhe Li1

  • 1Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York 10029, USA.

Nature Communications
|August 1, 2015
PubMed

Insights

Reticulon 1A (RTN1A) expression increases with chronic kidney disease (CKD) severity. Targeting RTN1A may reduce kidney damage by alleviating endoplasmic reticulum stress, offering a potential therapeutic strategy for CKD.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Biology

Background:

  • Chronic kidney disease (CKD) requires novel biomarkers and drug targets for improved therapies.
  • Reticulon 1 (RTN1) expression is investigated for its role in CKD progression.

Purpose of the Study:

  • To investigate the association between reticulon 1 (RTN1) expression and chronic kidney disease (CKD) severity.
  • To elucidate the role of RTN1A in endoplasmic reticulum (ER) stress and apoptosis in kidney cells.

Main Methods:

  • Isoform-specific expression analysis of RTN1 in diseased kidney tissues from mice and human patients.
  • In vitro studies involving RTN1 overexpression and knockdown in renal cells to assess ER stress and apoptosis.
  • In vivo studies in mouse models of kidney injury (unilateral ureteral obstruction and diabetic nephropathy) to evaluate the effect of Rtn1a knockdown.

Main Results:

  • An isoform-specific increase in RTN1A expression was detected in diseased kidneys, inversely correlating with renal function in diabetic nephropathy patients.
  • RTN1 overexpression induced ER stress and apoptosis in renal cells; RTN1 knockdown attenuated these effects.
  • RTN1A interacts with PERK, mediating ER stress.
  • In vivo Rtn1a knockdown reduced ER stress, renal fibrosis, proteinuria, glomerular hypertrophy, and mesangial expansion in mouse models.

Conclusions:

  • RTN1A is upregulated in CKD and contributes to disease progression by inducing ER stress.
  • RTN1A represents a potential therapeutic target for mitigating kidney disease progression.

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