Autophagosome protects proximal tubular cells from aldosterone-induced senescence through improving oxidative stress

Area of Science:

• Nephrology
• Cellular Biology
• Oxidative Stress Research

Background:

• Aldosterone significantly impacts proximal tubular cell (PTC) senescence, a key factor in renal dysfunction.
• Oxidative stress is a critical component in the pathology of chronic kidney diseases.

Purpose of the Study:

• To investigate the regulatory role of autophagy in aldosterone-induced PTC senescence via oxidative stress.
• To explore therapeutic potential of modulating autophagy in PTC injury.

Main Methods:

• Utilized both in vivo and ex vivo models of aldosterone-induced PTC senescence.
• Assessed senescence markers (SA-β-Gal, p21), oxidative stress (ROS, NOX4 expression), and autophagy flux (p62, LC3-II/LC3-I).
• Intervened with NOX4 siRNA, rapamycin (autophagy inducer), and chloroquine (autophagy inhibitor).

Main Results:

• Aldosterone treatment increased PTC senescence and oxidative stress, evidenced by elevated SA-β-Gal, ROS, NOX4, and p21.
• Aldosterone altered autophagic flux, indicated by changes in p62 and LC3-II/LC3-I.
• NOX4 inhibition or autophagy induction reduced oxidative stress and senescence; autophagy inhibition exacerbated these effects.

Conclusions:

• Autophagy plays a crucial role in regulating aldosterone-induced oxidative stress and senescence in PTCs.
• Modulating autophagy presents a promising therapeutic strategy for aldosterone-induced kidney injury by targeting oxidative stress.