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Fan Y, Zhang J, Xiao W, et al. Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy. Sci Rep. 2017;7(1):323doi: 10.1038/s41598-017-00305-6.
Fan, Y., Zhang, J., Xiao, W., Lee, K., Li, Z., Wen, J., He, L., Gui, D., Xue, R., Jian, G., Sheng, X., He, J. C., & Wang, N. (2017). Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy. Scientific reports, 7(1), 323. https://doi.org/10.1038/s41598-017-00305-6
Fan, Ying, et al. "Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy." Scientific reports vol. 7,1 (2017): 323. doi: https://doi.org/10.1038/s41598-017-00305-6
Fan Y, Zhang J, Xiao W, Lee K, Li Z, Wen J, He L, Gui D, Xue R, Jian G, Sheng X, He JC, Wang N. Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy. Sci Rep. 2017 Mar 23;7(1):323. doi: 10.1038/s41598-017-00305-6. PMID: 28336924; PMCID: PMC5428279.
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Sci Rep. 2017 Mar 23;7(1):323. doi: 10.1038/s41598-017-00305-6.

Rtn1a-Mediated Endoplasmic Reticulum Stress in Podocyte Injury and Diabetic Nephropathy.

Scientific reports

Ying Fan, Jing Zhang, Wenzhen Xiao, Kyung Lee, Zhengzhe Li, Jiejun Wen, Li He, Dingkun Gui, Rui Xue, Guihua Jian, Xiaohua Sheng, John Cijiang He, Niansong Wang

Affiliations

  1. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
  2. Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, NY, United States.
  3. Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, NY, United States. [email protected].
  4. Renal Section, James J Peter Veterans Administration Medical Center, Bronx, NY, United States. [email protected].
  5. Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. [email protected].

PMID: 28336924 PMCID: PMC5428279 DOI: 10.1038/s41598-017-00305-6

Abstract

We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress. We found increased expression of RTN1A and ER stress markers in the kidney of db/db-Unx mice. Treatment of TUDCA not only attenuated proteinuria and kidney histological changes, but also ameliorated podocyte and glomeruli injury in diabetic mice, which were associated with reduction of RTN1A and ER stress marker expression in the podocytes of TUDCA-treated mice. In vitro, we showed RTN1A mediates albumin-induced ER stress and apoptosis in human podocytes. A positive feedback loop between RTN1A and CHOP was found leading to an enhanced ER stress in podocytes. Our data suggest that ER stress plays a major role in podocyte injury in DN and RTN1A might be a key regulator of ER stress in podocytes.

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