The Role of Endoplasmic Reticulum Stress in Diabetic Nephropathy

Ying Fan, Kyung Lee, Niansong Wang, John Cijiang He

Research output: Contribution to journalReview articlepeer-review

82 Scopus citations

Abstract

Purpose of Review: Diabetic nephropathy (DN) has become the leading cause of end-stage renal disease (ESRD) worldwide. Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development and progression of DN. Recent findings suggested that many attributes of DN, such as hyperglycemia, proteinuria, and increased advanced glycation end products and free fatty acids, can all trigger unfolded protein response (UPR) in kidney cells. Herein, we review the current knowledge on the role of ER stress in the setting of kidney injury with a specific emphasis on DN. Recent Findings: As maladaptive ER stress response caused by excessively prolonged UPR will eventually cause cell death and increase kidney injury, several ER stress inhibitors have been shown to improve DN in animal models, albeit blocking both adaptive and maladaptive UPR. More recently, reticulon-1A (RTN1A), an ER-associated protein, was shown to be increased in both human and mouse diabetic kidneys. Its expression correlates with the progression of DN, and its polymorphisms are associated with kidney disease in people with diabetes. Increased RTN1A expression heightened the ER stress response and renal cell apoptosis, and conversely reduced RTN1A in renal cells decreased apoptosis and ameliorated kidney injury and DN progression, suggesting that RTN1A may be a novel target to specifically restrain the maladaptive UPR. Summary: These findings suggest that ER stress response in renal cells is a key driver of progression of DN and that the inhibition of the unchecked ER stress response in DN, such as by inhibition of RTN1A function, may be a promising therapeutic approach against DN.

Original languageEnglish
Article number17
JournalCurrent Diabetes Reports
Volume17
Issue number3
DOIs
StatePublished - 1 Mar 2017

Keywords

  • Apoptosis
  • Diabetic nephropathy
  • Endoplasmic reticulum stress
  • Reticulon-1 (RTN-1)
  • Unfolded protein response

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