Abstract: SA-PO286
Chronic Intermittent Hypoxia Aggravates Progression of Diabetic Nephropathy via Inducing Endoplasmic Reticulum Stress and Mitochondrial Dysfunction
Session Information
- Diabetic Kidney Disease: Basic - 2
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Jia, Junjie, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Feng, Haoran, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wang, Niansong, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Fan, Ying, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common complication of diabetic nephropathy (DN), which has been found to exacerbate the progression of DN. Chronic intermittent hypoxia (CIH) is one of the most important pathophysiological mechanisms of OSAHS, but its exact impact on DN remains unknown.
Methods
Renal biopsy specimens and the clinical data of 18 biopsy-proven DN patients were collected to observe the correlation of the severity of OSAHS in these patients with their renal function indexes and renal pathological damage. An animal model of DN combined with OSAHS was established by subjecting type 2 diabetic db/db mice to in vivo CIH stimulation for 12 weeks. RNA-sequencing was performed on the kidney cortex tissue from mice to identify the factors CIH mediating the progression of DN. In vitro, HK-2 cells were induced by high glucose (HG) combined with CIH stimulation to confirm the effect of CIH on diabetic tubular injury.
Results
In the current study, we found that the severity of OSAHS was significantly correlated with renal function decline and tubular pathological damage in biopsy-proven DN patients. In vivo, the kidney damage, especially renal tubular injury of the 12-week-CIH-stimulating db/db mice was more severe as compared to normoxic controlled db/db mice and wild-type littermates. RNA-sequencing revealed that increased severity of tubular injury caused by CIH might be associated with activated endoplasmic reticulum stress (ERS), mitochondrial dysfunction, and the exacerbation of apoptosis as well. The in vitro experiments confirmed the results, demonstrating that HK-2 cells treated with HG combined CIH exhibited worsened cell apoptosis, ERS, and mitochondrial dysfunction.
Conclusion
This is the first basic research study to investigate the impact of OSAHS on the progression of DN. Our findings show that OSAHS is an important risk factor for the deterioration of renal function and aggravated tubular damage in the course of DN, in which the mechanism is related to the exacerbation of ERS and mitochondrial dysfunction caused by CIH.