Related Experiment Video
Updated: Mar 14, 2026
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury,
1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Clinical Center for Sleep Breathing Disorder and Snoring, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Abstract:
Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.
Insights
Obstructive sleep apnea causes kidney damage via chronic intermittent hypoxia. Soluble RAGE (sRAGE) treatment reduced inflammation and apoptosis in a rat model, suggesting therapeutic potential for kidney injury.
Area of Science:
- Nephrology
- Sleep Medicine
- Molecular Biology
Background:
- Obstructive sleep apnea (OSA) is linked to chronic kidney disease (CKD).
- Chronic intermittent hypoxia (CIH) in OSA triggers tissue damage.
- Receptor for advanced glycation end product (RAGE) and high mobility group box 1 (HMGB1) mediate inflammation in OSA-related diseases.
Purpose of the Study:
- To investigate the roles of RAGE and HMGB1 in CIH-induced renal injury.
- To evaluate the therapeutic effect of soluble RAGE (sRAGE) on inflammation and apoptosis in a CIH rat model.
Main Methods:
- Rats were exposed to normal air (NA) or CIH, with or without sRAGE administration.
- Renal histological injury, RAGE-HMGB1 levels, and inflammatory/apoptotic pathways were assessed.
- Tubular endothelial apoptosis was determined using CD31 and TUNEL staining.
Main Results:
- CIH induced renal histological injury and upregulated RAGE-HMGB1, NF-κB, TNF-α, IL-6, and altered Bcl-2/Bax and MAPK pathways.
- sRAGE treatment abolished most CIH-induced changes, except for p-ERK.
- sRAGE attenuated tubular endothelial apoptosis and improved renal function.
Conclusions:
- RAGE-HMGB1 signaling contributes to CIH-induced renal injury pathogenesis.
- sRAGE shows therapeutic potential for CIH-induced kidney injury by inhibiting RAGE-HMGB1 interactions via P38 and JNK pathways.
