Cordyceps cicadae Prevents Renal Tubular Epithelial Cell Apoptosis by Regulating the SIRT1/p53 Pathway in Hypertensive Renal Injury.

Yi Shan Huang,Xueting Han,Zebing Zhu,Xu Wang,Wei Jing Liu,Zhendong Feng,Hailan Cui,Yu Ning Liu,Chenhui Xia

doi:10.1155/2020/7202519

Abstract

Hypertensive renal injury is a primary etiology of end-stage renal disease, and satisfactory therapeutic strategies are urgently required. Cordyceps cicadae, a traditional Chinese herb, has potential renoprotective benefits and is widely used in the treatment of many kidney diseases. To investigate the mechanisms underlying the renoprotective effect of C. cicadae on hypertensive renal injury, we studied the effect of C. cicadae on tubular epithelial cells (TECs) in a spontaneously hypertensive rat (SHR) model and angiotensin II- (AngII-) cultured primary TECs. Our study showed that C. cicadae treatment could decrease 24-hour urine albumin, albumin-to-creatinine ratio (ACR), β2-MG level, and kidney injury molecule-1 (kim-1) level in SHR urine, alleviate interstitial fibrosis, and reduce α-smooth muscle actin (α-SMA) expression in SHR kidney. In primary TECs, medicated serum containing C. cicadae (CSM) might significantly reduce the AngII-induced production of kim-1 and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, C. cicadae treatment could decrease TEC apoptosis in SHRs as assessed by the terminal transferase-mediated biotin dUTP nick-end labeling (TUNEL) assay. CSM could inhibit caspase-3 activity and enhance cellular viability as measured by methyl thiazolyl tetrazolium in AngII-cultured TECs, suggesting that CSM might reduce the apoptosis level in TECs induced by AngII. We found that the SIRT1 expression level was markedly lowered, while the protein level of acetylated-p53 was elevated in the TECs of patients with hypertensive renal injury and SHRs. C. cicadae presented the effect of regulating the SIRT1/p53 pathway. Further SIRT1 inhibition with EX527 reversed the effect of C. cicadae on AngII-induced apoptosis. Taken together, our results indicate that C. cicadae offers a protective effect on TECs under hypertensive conditions, which may be related to its antiapoptotic effect through regulation of the SIRT1/p53 pathway.

Highlights

Hypertensive renal injury is a serious complication of hypertension, which is second to diabetic kidney disease as a key etiology of end-stage renal disease [1]. e pathogenesis of hypertensive renal injury includes activation of the renin-angiotensin-aldosterone system (RAAS), increased arteriosclerosis, elevated sympathetic nervous activity, and water-sodium retention by the kidney [2]
Our results indicate that C. cicadae offers a protective effect on tubular epithelial cells (TECs) under hypertensive conditions, which may be related to its antiapoptotic effect through regulation of the Silent information regulator homolog 1 (SIRT1)/p53 pathway
Blood pressures (BPs) was remarkably higher in the spontaneously hypertensive rat (SHR) than in the WKY rats, while C. cicadae treatment had no effect on BP (Table 1). e SHRs exhibited high Blood urea nitrogen (BUN) levels, as well as increased 24-hour urine albumin, albumin-to-creatinine ratio (ACR), and β2-MG levels at week 28 (Figures 1(a)–1(c) and 1(e)), while the serum creatinine level and 24-hour urine protein showed no significant difference (Figures 1(d) and 1(f ))

Summary

Introduction

Hypertensive renal injury is a serious complication of hypertension, which is second to diabetic kidney disease as a key etiology of end-stage renal disease [1]. e pathogenesis of hypertensive renal injury includes activation of the renin-angiotensin-aldosterone system (RAAS), increased arteriosclerosis, elevated sympathetic nervous activity, and water-sodium retention by the kidney [2]. E pathogenesis of hypertensive renal injury includes activation of the renin-angiotensin-aldosterone system (RAAS), increased arteriosclerosis, elevated sympathetic nervous activity, and water-sodium retention by the kidney [2]. Agents targeting these pathways, such as RAAS blockers and diuretics, may not completely prevent the development of hypertensive kidney injury. Recent studies have identified that tubular epithelial cell (TEC) apoptosis plays an important role in the progression of renal tubulointerstitial fibrosis [4,5,6], as well as in the pathogenesis and progression of hypertensive renal injury [7,8,9]. The role of the SIRT1/p53 pathway in the mechanism of hypertensive renal injury has yet to be examined

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Discussion

Conclusion