Abstract：
Urine-derived renal epithelial cells (URECs) are highly voided after kidney transplant and express typical kidney markers, including markers of kidney epithelial progenitor cells. Recently URECs have shown promising immunomodulatory properties when cultured with Peripheral Blood Mononuclear Cells (PBMCs), promoting an increase in the T regulatory cells. In vivo, kidney cells are highly exposed to damage associated molecules during both acute and chronic kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most -known early marker of acute and chronic kidney damage. However, its role on the evolution of renal damage has not yet been fully described, nor has its impact on the characteristics of renal-derived cells during in vitro culture. The aim of this study is to investigate the effect of NGAL on the characteristics of URECs isolated after kidney transplant, by exposing these cells to the treatment with NGAL during in vitro culture and evaluating its effect on UREC viability, proliferation, and immunomodulatory potential. The exposure of URECs to NGAL reduced their viability and proliferative capacity, promoting the onset of apoptosis. The immunomodulatory properties of URECs were partially inhibited by NGAL, without affecting the increase of Treg cells observed during UREC-PBMCs coculture. These results suggest that the exposure to NGAL may compromise some features of kidney stem and specialized cell types, reducing their viability, increasing apoptosis, and partially altering their immunomodulatory properties. Thus, NGAL could represent a target for approaches acting on its inhibition or reduction to improve functional recovery.
摘要：
尿液来源的肾上皮细胞（UREC）在肾移植后高度排泄，表达典型的肾脏标志物，包括肾上皮祖细胞的标记。最近，当与外周血单核细胞（PBMC）一起培养时，UREC已显示出有希望的免疫调节特性，促进T调节细胞的增加。在体内,肾细胞在急性和慢性肾损伤期间都高度暴露于损伤相关分子。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是最已知的急性和慢性肾损害的早期标志物之一。然而,其对肾脏损害演变的作用尚未完全描述，在体外培养过程中对肾源性细胞的特性也没有影响。这项研究的目的是研究NGAL对肾移植后分离的UREC特征的影响，通过在体外培养期间将这些细胞暴露于NGAL处理并评估其对UREC活力的影响，扩散,和免疫调节潜力。UREC暴露于NGAL降低了它们的活力和增殖能力，促进细胞凋亡的开始。UREC的免疫调节特性被NGAL部分抑制，不影响在UREC-PBMC共培养期间观察到的Treg细胞的增加。这些结果表明，暴露于NGAL可能会损害肾脏干细胞和特殊细胞类型的某些特征，降低他们的生存能力，增加细胞凋亡，并部分改变了它们的免疫调节特性。因此，NGAL可以代表作用于其抑制或减少以改善功能恢复的方法的靶标。
