Elucidation of the relationship between autophagy and glomerulosclerosis caused by podocyte injury

GABARAP（γ-氨基丁酸A受体相关蛋白）最近被鉴定为自噬相关蛋白，尽管其在自噬中的确切作用尚不清楚。我们最近产生的绿色荧光蛋白（GFP）-GABARAP转基因（Tg）小鼠，其中GFP-GABARAP在肾小球足细胞中大量表达。与野生型（WT）小鼠相比，阿霉素（ADR）治疗导致Tg小鼠蛋白尿和肾小球硬化显著增加。我们的研究结果表明，GABARAP是负责肾小球功能的损害，它阻碍了恢复的影响ADR.Next，我们产生足细胞特异性Atg 7敲除（KO）小鼠，其中自噬被抑制。ADR治疗对KO小鼠的足细胞损伤明显比WT小鼠严重。目前，我们正在继续阐明足细胞损伤与足细胞自噬缺陷之间的关系。

GABARAP (gamma-aminobutyric acid A receptor-associated protein) has recently been characterized as an autophagy related protein, though its precise role in autophagy remains unclear. We recently generated green fluorescent protein (GFP)-GABARAP transgenic (Tg) mice, in which GFP-GABARAP is abundantly expressed in glomerular podocytes. Adriamycin (ADR) treatment which causes glomerulosclerosis resulted in a significant increase in proteinuria and sclerotic glomeruli in Tg mice when compared to wild type (WT) mice. Our results indicate that GABARAP is responsible for the impairment of glomerular function, and that it retards recovery from the effects of ADR.Next, we produced podocyte-specific Atg7 knockout (KO) mice in which autophagy is suppressed. ADR treatment produced significantly worse podocyte injury to KO mice than to WT mice.Presently, we are continuing to elucidate the relationship between podocyte injury and autophagy deficiency in the podocyte.