Non-lethal sonodynamic therapy mitigates hypertensive renal fibrosis through the PI3K/AKT/mTORC1-autophagy pathway.

Hypertension constitutes a significant public health concern, characterized by a high incidence and mortality rate. Hypertensive kidney disease is a prevalent complication associated with hypertension and is the second leading cause of end-stage renal disease (ESRD). Renal fibrosis linked to hypertension has emerged as the third leading cause of disease in dialysis patients. Autophagy activity is crucial for maintaining homeostasis, vitality, and physiological function of kidney cells, while also protecting the kidneys from fibrosis. The deficiency of autophagy will increase the sensitivity of the kidney to the damage, leading to impaired renal function, accumulation of damaged mitochondria and more severe of renal fibrosis. However, enhancing autophagy by activating the PI3K/AKT, AMPK, and mTOR pathways, improves podocyte injury and renal pathological changes, and ameliorates renal function. Current clinical interventions aimed at halting or reversing renal fibrosis in hypertensive patients are notably limited in their efficacy. Here, we present Non-lethal Sonodynamic Therapy (NL-SDT), in which ultrasound is used to activate locally sonosensitizers, thereby stimulating the production of reactive oxygen species for the purpose of modulating cell function or fate, as a novel methodology to inhibit progression of hypertensive renal fibrosis.To confirm whether NL-SDT can reduce hypertensive renal fibrosis and its mechanism. The mice model of hypertensive renal fibrosis was established by using osmotic minipumps (Alzet model 2004, Cupertino, CA) equipped with angiotensin-II (Ang II). The pumps were implanted in mice, ensuring constant infusion of Ang II at a dose of 1.0 µg/kg per minute for 4 weeks. The mice were exposed to 0.4 W/cm