Role of TGF-β1/Smad3 signalling pathway in renal tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension induced by increased pulse pressure.

Abstract

Objective: Elevated systolic blood pressure and increased pulse pressure are closely associated with renal damage; however, the exact mechanism remains unclear. Therefore, we investigated the effects of increased pulse pressure on tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension (ISH). Additionally, the role of renal tubular epithelial-mesenchymal transition (EMT) and its upstream signalling pathways were elucidated.

Methods: Ten-month-old male rats were randomly divided into control and ISH groups, with seven rats in each group administered warfarin and vitamin K1 for 6 weeks. Blood pressure, renal function, mean blood flow in the common iliac artery, and diastolic vessel diameter were assessed, and the rat kidney medulla was collected for histological, genetic, and protein level analysis.

Results: Increased pulse pressure, abnormal renal function, and increased shear stress were detected in rats with ISH. Histology assessments revealed fibrosis in the interstitium of ISH rats. Epithelial marker E-cadherin protein expression was decreased, while the protein expression of interstitial markers α-SMA and Vimentin was increased, and transforming growth factor (TGF)-β1/Smad3 signalling was upregulated in the kidney tissue of ISH rats.

Conclusions: Increased pulse pressure in elderly rats with ISH caused an increase in shear stress. These effects led to the development of EMT and the activation of its upstream TGF-β1/Smad3 signalling pathway, ultimately leading to renal tubular interstitial fibrosis causing renal injury.