Daily Low-intensity Pulsed Ultrasound Ameliorates Renal Fibrosis and Inflammation in Experimental Hypertensive and Diabetic Nephropathy

被引:23
作者
Aibara, Yoshiki [1 ]
Nakashima, Ayumu [1 ,2 ]
Kawano, Ki-ichiro [1 ]
Yusoff, Farina Mohamad [1 ]
Mizuki, Fumitaka [1 ]
Kishimoto, Shinji [1 ]
Kajikawa, Masato [3 ]
Maruhashi, Tatsuya [1 ]
Higashi, Yukihito [1 ,3 ]
机构
[1] Hiroshima Univ, Dept Cardiovasc Regenerat & Med, Res Inst Radiat Biol & Med, Hiroshima, Japan
[2] Hiroshima Univ, Dept Stem Cell Biol & Med, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan
[3] Hiroshima Univ Hosp, Div Regenerat & Med, Med Ctr Translat & Clin Res, Hiroshima, Japan
关键词
fibrosis; hypertensive nephropathy; mice; nephrectomy; proteinuria; ISCHEMIA-REPERFUSION INJURY; MOUSE MODEL; OXIDATIVE STRESS; KIDNEY-DISEASE; DYSFUNCTION; LIPUS; CELLS;
D O I
10.1161/HYPERTENSIONAHA.120.15237
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
The estimated morbidity rate of chronic kidney disease is 8% to 16% worldwide, and many patients with chronic kidney disease eventually develop renal failure. Thus, the development of new therapeutic strategies for preventing renal failure is crucial. In this study, we assessed the effects of daily low-intensity pulsed ultrasound (LIPUS) therapy on experimental hypertensive nephropathy and diabetic nephropathy. Unilateral nephrectomy and subcutaneous infusion of angiotensin II via osmotic mini-pumps were used to induce hypertensive nephropathy in mice. Immunohistochemistry revealed that daily LIPUS treatment ameliorated renal fibrosis and infiltration of inflammatory cells induced by angiotensin II. A similar therapeutic effect was also observed in mice with angiotensin II-induced hypertensive nephropathy in which splenectomy was performed. In addition, LIPUS treatment significantly decreased systolic blood pressure after 21 days. Subsequently, db/db mice with unilateral nephrectomy developed proteinuria; daily LIPUS treatment significantly reduced proteinuria after 42 days. In addition, immunohistochemistry revealed that renal fibrosis was significantly ameliorated by LIPUS treatment. Finally, LIPUS stimulation suppressed TGF-beta 1 (transforming growth factor-beta 1)-induced phosphorylation of Smad2 and Smad3 in HK-2 (human proximal tubular cell line) cells. LIPUS treatment may be a useful therapy for preventing the progression of renal fibrosis in patients with chronic kidney disease.
引用
收藏
页码:1906 / 1914
页数:9
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