Mei Shuqin, Livingston Man, Hao Jielu, Li Lin, Mei Changlin, Dong Zheng
Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University and Charlie Norwood VA Medical Center, Augusta, Georgia.
Sci Rep. 2016 Feb 26;6:22171. doi: 10.1038/srep22171.
Endotoxemia in sepsis, characterized by systemic inflammation, is a major cause of acute kidney injury (AKI) in hospitalized patients, especially in intensive care unit; however the underlying pathogenesis is poorly understood. Autophagy is a conserved, cellular catabolic pathway that plays crucial roles in cellular homeostasis including the maintenance of cellular function and viability. The regulation and role of autophagy in septic or endotoxic AKI remains unclear. Here we show that autophagy was induced in kidney tubular cells in mice by the endotoxin lipopolysaccharide (LPS). Pharmacological inhibition of autophagy with chloroquine enhanced LPS-induced AKI. Moreover, specific ablation of autophagy gene 7 (Atg7) from kidney proximal tubules worsened LPS-induced AKI. Together, the results demonstrate convincing evidence of autophagy activation in endotoxic kidney injury and support a renoprotective role of autophagy in kidney tubules.
脓毒症中的内毒素血症以全身炎症为特征，是住院患者尤其是重症监护病房患者急性肾损伤（AKI）的主要原因；然而，其潜在发病机制尚不清楚。自噬是一种保守的细胞分解代谢途径，在细胞稳态中发挥关键作用，包括维持细胞功能和活力。自噬在脓毒症或内毒素血症诱导的急性肾损伤中的调节和作用仍不清楚。在这里，我们表明内毒素脂多糖（LPS）可诱导小鼠肾小管细胞发生自噬。用氯喹对自噬进行药理学抑制可增强LPS诱导的急性肾损伤。此外，从肾近端小管特异性敲除自噬基因7（Atg7）会使LPS诱导的急性肾损伤恶化。总之，这些结果证明了内毒素性肾损伤中自噬激活的令人信服的证据，并支持自噬在肾小管中的肾保护作用。
