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Abstract: FR-PO997

ALDH2 Expression Is Reduced in Human and Mouse Renal Tissue Following CKD

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Chiu, Ijen, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Ajay, Amrendra Kumar, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Shah, Kavya Mehul, Harvard Medical School, Boston, Massachusetts, United States
  • Hsiao, Li-Li, Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Chronic kidney disease (CKD) poses a tremendous socioeconomic burden in addition to increasing rates of morbidity and mortality, and several East Asian countries have a much higher prevalence of CKD compared to the global average. The ALDH2 E504K polymorphism is found in 35-45% of East Asian populations and has been linked to a higher risk of various cardiovascular diseases, neurological disorders, and cancers. However, despite the high prevalence of the ALDH2 polymorphism and of CKD among East Asian populations, little is known about the role of ALDH2 in CKD.

Methods

ALDH2 expression patterns in kidney tissue were determined via immunohistochemical staining of mouse kidneys and human kidney biopsy samples. To explore the role of ALDH2 in CKD, ALDH2 expression was studied in vivo using an aristolochic acid-induced CKD mouse model and in vitro via human renal proximal tubular epithelial cells (RPTECs). RPTECs were further utilized and cultured with the profibrotic protein TGF-β to investigate the role of ALDH2 in kidney fibrosis.

Results

ALDH2 was highly expressed in the renal proximal tubules of healthy human and mouse kidneys. ALDH2 expression was significantly downregulated in CKD patients and inversely correlated with the severity of CKD, in human and mouse studies. Mechanistically, it was demonstrated that a deficiency in ALDH2 expression was associated with kidney fibrosis in vitro, due to the role of ALDH2 protein in modulating the epithelial-mesenchymal transition.

Conclusion

ALDH2 has a specific and localized expression pattern in the kidneys, and a deficiency in ALDH2 expression is linked to kidney fibrosis. These findings may have significant clinical implications in the development and progression of kidney disease, especially among East Asian populations.

Funding

  • Other NIH Support