Salusin-β is abundantly expressed in many organs and tissues including heart, blood vessels, brain and kidneys. Recent studies have identified salusin-β as a bioactive peptide that contributes to various diseases, such as atherosclerosis, hypertension, diabetes and metabolic syndrome. However, the role of salusin-β in the pathogenesis of acute kidney injury (AKI) is largely unclear. In the present study, we investigated the roles of salusin-β in cisplatin or lipopolysaccharide (LPS)-induced renal injury. Herein, we found that salusin-β expression was upregulated in both renal tubular cells and kidney tissues induced by both cisplatin and LPS. In vitro, silencing of salusin-β diminished, whereas overexpression of salusin-β exaggerated the increased PKC phosphorylation, oxidative stress, histone γH2AX expression, p53 activation and apoptosis in either cisplatin or LPS-challenged renal tubular cells. More importantly, salusin-β overexpression-induced tubular cell apoptosis were abolished by using the PKC inhibitor Go 6976, reactive oxygen species (ROS) scavenger NAC, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin (Apo) or p53 inhibitor Pifithrin-α. In animals, blockade of salusin-β alleviated PKC phosphorylation, ROS accumulation, DNA damage, and p53 activation as well as renal dysfunction in mice after administration of cisplatin or LPS. Taken together, these results suggest that overexpressed salusin-β is deleterious in AKI by activation of the PKC/ROS signaling pathway, thereby priming renal tubular cells for apoptosis and death.

Salusin-β在心脏，血管，脑和肾脏等许多器官和组织中大量表达。最近的研究已将salusin-β鉴定为一种生物活性肽，可导致多种疾病，例如动脉粥样硬化，高血压，糖尿病和代谢综合征。但是，salusin-β在急性肾损伤（AKI）发病机理中的作用尚不清楚。在本研究中，我们调查了salusin-β在顺铂或脂多糖（LPS）诱导的肾损伤中的作用。在本文中，我们发现顺铂和LPS诱导的肾小管细胞和肾组织中salusin-β的表达均被上调。体外，salusin-β的沉默减弱，而salusin-β的过度表达则夸大了顺铂或LPS攻击的肾小管细胞中PKC磷酸化，氧化应激，组蛋白γH2AX表达，p53活化和凋亡的增加。更重要的是，通过使用PKC抑制剂Go 6976，活性氧（ROS）清除剂NAC，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂阿波西宁（Apo）或p53抑制剂Pifithrin-α，消除了salusin-β过表达诱导的肾小管细胞凋亡。在动物中，salusin-β的阻滞减轻了顺铂或LPS给药后小鼠的PKC磷酸化，ROS积累，DNA损伤和p53活化以及肾功能障碍。在一起