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Published on: November 7, 2017
Cathepsin S Deficiency Prevents Chronic Stress-Related Renal Remodeling and Dysfunction in a Mouse 5/6 Nephrectomy
Hailong Wang1,2, Shengnan Xu3, Xiangkun Meng4
1Department of Cardiology and Hypertension, The Affiliated Hospital of Yanbian University (Yanbian Hospital), Yanji, Jilin, China.
Summary
Chronic stress worsens kidney disease. Cathepsin S (CatS) drives this damage by increasing inflammation, oxidative stress, and apoptosis. Inhibiting CatS may offer a new treatment for kidney disease patients experiencing stress.
Area of Science:
- Nephrology
- Pathobiology
- Stress Physiology
Background:
- Chronic psychological stress is a known factor that exacerbates chronic kidney disease (CKD).
- Lysosome cathepsins are implicated in human diseases, prompting investigation into their specific roles in stress-induced kidney damage.
- Cathepsin S (CatS) is a lysosomal protease whose role in the context of chronic stress and CKD requires elucidation.
Purpose of the Study:
- To investigate the role of cathepsin S (CatS) in exacerbating renal damage and dysfunction caused by chronic restrain stress (CRS) in a mouse model of chronic kidney disease (CKD).
- To explore the potential of CatS as a therapeutic target for mitigating stress-related renal injury and hypertension in CKD.
Main Methods:
- A 5/6 nephrectomy (5/6Nx) mouse model was combined with chronic restrain stress (CRS).
- Studies utilized wild-type (CatS+/+) and CatS knockout (CatS-/-) mice, alongside pharmacological CatS inhibition.
- Renal function, blood pressure, histological alterations, and molecular markers of inflammation, oxidative stress, and apoptosis were assessed.
Main Results:
- CRS significantly worsened 5/6Nx-induced renal injury, hypertension, glomerulosclerosis, fibrosis, podocyte damage, and macrophage infiltration, correlating with increased renal CatS expression.
- CatS knockout mice and those treated with CatS inhibitors showed attenuated CRS-induced renal injury, improved renal function, and reduced blood pressure.
- Reduced levels of inflammatory markers, oxidative stress proteins, apoptotic factors, and extracellular matrix remodeling proteins were observed in CatS-deficient or inhibited mice.
- In vitro studies confirmed CatS's role in mediating apoptosis in mesangial cells.
Conclusions:
- Cathepsin S (CatS) plays a critical role in mediating the exacerbation of renal injury and hypertension induced by chronic psychological stress in the context of CKD.
- CatS inhibition ameliorates stress-induced renal damage by reducing oxidative stress, inflammation, proteolysis, and apoptosis.
- CatS represents a promising therapeutic target for managing stress-related renal complications and hypertension in CKD patients.
