Rezzani Rita, Franco Caterina, Favero Gaia, Rodella Luigi F
Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia Brescia, Italy.
Interdipartimental University Center of Research "Adaptation and Regeneration of Tissues and Organs-(ARTO)", University of Brescia Brescia 25123, Italy.
Am J Transl Res. 2019 Jul 15;11(7):4263-4276. eCollection 2019.
Renal diseases interfere with the regulation of several metabolic pathways including dyslipidemia. The latter includes increased triglycerides, very low-density lipoprotein levels and decreased high-density lipoproteins. These lipoproteins change during renal injury. Apolipoprotein-E deficient mice (ApoE) are considered a very well accepted model of hypercholesterolemia with marked renal pathological alterations. Ghrelin hormone is mainly secreted from the stomach when the stomach is empty, but it is also found in the kidney. In this organ it has autocrine and/or paracrine roles determining glomerular filtration rate, tubular phosphate and sodium reabsorption. Interestingly, it has been demonstrated that ghrelin levels increase after fasting. This mechanism induces an interaction with sirtuin 1 (SIRT1)/p53 pathway suggesting a link between ghrelin and SIRT1 in the regulation of salt and water metabolism. The mechanisms of ghrelin-induced SIRT1 expression are not yet fully understood. Recent studies indicate that SIRT1 exerts renoprotective properties against kidney diseases. This could be a very interesting point for underlining the important role of the ghrelin-SIRT1 system. Water movement across biological cell membranes is enhanced or facilitated by tetrameric membrane-bound channels, named aquaporin (AQP) family, and in particular, AQP1 and AQP2 proteins. In this study, we evaluated the possible pathway existing among the ghrelin/SIRT1/AQP1/AQP2 system in APOE mice in order to clarify or stress the role played by said system in renal diseases associated to aging with or without comorbities. The results could provide a basis for considering ghrelin as a new target for therapeutic strategies of renal injury.
肾脏疾病会干扰包括血脂异常在内的多种代谢途径的调节。后者包括甘油三酯增加、极低密度脂蛋白水平升高以及高密度脂蛋白降低。这些脂蛋白在肾损伤期间会发生变化。载脂蛋白E缺陷小鼠（ApoE）被认为是一种被广泛接受的高胆固醇血症模型，伴有明显的肾脏病理改变。胃饥饿素主要在胃排空时从胃中分泌，但在肾脏中也有发现。在这个器官中，它具有自分泌和/或旁分泌作用，决定肾小球滤过率、肾小管磷酸盐和钠的重吸收。有趣的是，已经证明禁食后胃饥饿素水平会升高。这种机制诱导了与沉默调节蛋白1（SIRT1）/p53途径的相互作用，表明胃饥饿素和SIRT1在盐和水代谢调节中存在联系。胃饥饿素诱导SIRT1表达的机制尚未完全了解。最近的研究表明，SIRT1对肾脏疾病具有肾脏保护特性。这可能是强调胃饥饿素-SIRT1系统重要作用的一个非常有趣的点。水通过名为水通道蛋白（AQP）家族的四聚体膜结合通道，特别是AQP1和AQP2蛋白，在生物细胞膜上的移动得到增强或促进。在本研究中，我们评估了ApoE小鼠中胃饥饿素/SIRT1/AQP1/AQP2系统之间可能存在的途径，以阐明或强调该系统在伴有或不伴有合并症的与衰老相关肾脏疾病中所起的作用。这些结果可为将胃饥饿素视为肾损伤治疗策略的新靶点提供依据。
