ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO372

The Analysis of Chaperone-Mediated Autophagy in Hypertensive Kidney Disease

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Nakatani, Yoshihisa, Division of Nephrology, Department of Internal Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
  • Takami, Masahiro, Division of Nephrology, Department of Internal Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
  • Arima, Shuji, Division of Nephrology, Department of Internal Medicine, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
Background

Three different types of autophagy coexist in mammalian various cells. Chaperone-mediated autophagy (CMA) in kidney disease such as acute kidney injury and diabetic nephropathy has been reported. However, it is unclear whether CMA is involved in hypertensive kidney disease. So we examined whether CMA is involved in hypertensive renal disease and its mechanism.

Methods

First, we examined CMA levels in WKY (Wister Kyoto Rat) and MSHRSP (Malignant Stroke-Prone Spontaneously Hypertensive Rat) and treated with antihypertensive therapy by extracting lysosome fractions and using immunoprecipitation.
In fact analysis of hypertensive model rats revealed that Lamp2A was strongly expressed in the proximal tubule and collecting duct, and co-staining with Hsc70 was also observed and could confirmed CMA.
Therefore by using HK2 cells treated with endoplasmic reticulum stress (ERS) chemical inducer tunicamysin (Tun), we examined cell damage and mitochondrial injury if CMA was regulated by siRNA, Trichostatin A (TSA) and Humanin (HMN).

Results

First, compared with WKY, lysosome-Lamp2A expression was significantly increased in the renal medulla of MSHRSP but not in the renal cortex of MSHRSP. By antihypertensive therapy, ly-Lamp2A expression was significantly increased and CMA activity upregulated, so CMA failure was confirmed.
Second, in HK2 cell with treated Tun, CMA was rapidly increased at 1 hour of administration and lasted for 3 hours. After12 hours, CMA activity returned to the initial condition, and at 24 hours, it decreased to about 50 percentages. When expression was reduced in Hsc70 and Lamp2, CMA decreased and cell induced apoptosis. In addition, in TSA treatment which involved in Hsc70 transport, ly-Lamp2A did not change and almost no CMA occurred. In HMN treatment such as CMA enhancer, pAKT was increased, but Bax and pJNK were also increased in lysosome, we would be able to consider that ERS induced CMA ameliorates cell damage, but it also seems to increase apoptosis of unnecessary abnormal mitochondria and damaged cells.

Conclusion

We found CMA induced ERS pathway was associated with cell apoptosis and mitochondria injury in hypertensive kidney disease.