Journal Article

MICT ameliorates hypertensive nephropathy by inhibiting TLR4/NF-κB pathway and down-regulating NLRC4 inflammasome

Chen, Xinhua, Luo, Minghao, Li, Lingang, Chang, Qing, Li, Yun, Dong, Wenyu

2024

Overview

Hypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear. The spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model. MICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells. MICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Angiotensin II / Animals / Antigens / Biology and Life Sciences / Blood pressure / Calcium-Binding Proteins - metabolism / Cell activation / Cytokines / Down-Regulation / End-stage renal disease / Exercise Therapy - methods / Fibrosis / Fitness training programs / Heart rate / Humans / Hypertension / Hypertension, Renal - metabolism / Hypertension, Renal - pathology / Immune system / Inflammasomes / Inflammasomes - metabolism / Inflammation / Inflammatory response / Kidney - metabolism / Kidney - pathology / Kidney diseases / Kidneys / Laboratory animals / Male / Medicine and Health Sciences / Membranes / Morbidity / Nephritis - metabolism / Nephritis - pathology / Nephropathy / NF-kappa B - metabolism / NF-κB protein / Pathogenesis / Pathogens / Physical training / Proteins / Rats / Rats, Inbred SHR / Renal function / Signal Transduction / TLR4 protein / Toll-Like Receptor 4 - metabolism / Toll-like receptors / Training