Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, P.R. China.
PLoS One. 2024 Sep 6;19(9):e0310001. doi: 10.1371/journal.pone.0310001. eCollection 2024.
Obstructive uropathy is a common kidney disease caused by elevated hydrostatic pressure (HP), but relevant molecular and cellular mechanisms have not yet been well understood. In this study, we ex vivo investigated the effects of elevated HP on human renal epithelial cells (HREpCs). Primary HREpCs were subjected to 100 cmH2O HP for 8 or 48 h. Then, the cells were cultured without HP stimulation for another 24 h or 72 h. Cell morphology showed almost no change after 8h HP treatment, but exhibited reversible elongation after 48h HP treatment. HP treatment for 8 h increased the expression of TGFB1 and VEGFA but decreased the expression of CSF2 and TGFB2. On the other hand, HP treatment for 48 h downregulated the expression of CSF2, TGFB2, PDGFB, VEGFA, and VEGFB, while upregulated the expression of TGFB3. Interestingly, all changes induced by 48 h HP treatment were detected more severe compared to 8 h HP treatment. In conclusion, elongated ex vivo HP loading to renal epithelial cells induces reversible changes on cell morphology and disturbs the expression of several growth factors, which provides novel mechanistic insight on elevated HP-caused kidney injury such as obstructive uropathy.
梗阻性尿路病是一种常见的肾脏疾病,由静水压力升高引起,但相关的分子和细胞机制尚未得到很好的理解。在这项研究中,我们在体外研究了升高的静水压力对人肾上皮细胞(HREpC)的影响。原代 HREpC 被置于 100cmH2O 的静水压力下 8 或 48 小时。然后,细胞在没有 HP 刺激的情况下再培养 24 或 72 小时。细胞形态在 8 小时 HP 处理后几乎没有变化,但在 48 小时 HP 处理后表现出可逆的伸长。HP 处理 8 小时增加了 TGFB1 和 VEGFA 的表达,但降低了 CSF2 和 TGFB2 的表达。另一方面,HP 处理 48 小时下调了 CSF2、TGFB2、PDGFB、VEGFA 和 VEGFB 的表达,同时上调了 TGFB3 的表达。有趣的是,与 8 小时 HP 处理相比,48 小时 HP 处理诱导的所有变化都更为严重。总之,体外拉长 HP 负荷到肾上皮细胞上会引起细胞形态的可逆变化,并扰乱几种生长因子的表达,这为梗阻性尿路病等由升高的 HP 引起的肾脏损伤提供了新的机制见解。