Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis.
Epidermal growth factor receptor promotes glomerular injury and renal failure in rapidly progressive crescentic glomerulonephritis.
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急进性肾小球肾炎（Rapidly progressive glomerulonephritis，RPGN）是肾小球严重损伤的一种形态学表现.肾小球损伤表现为增殖性组织学模式（“新月体”），伴随T细胞和巨噬细胞的积聚以及固有肾小球细胞的增殖。我们显示从头诱导肝素结合表皮生长因子样生长因子（HB-EGF）在内源性肾小球上皮细胞（足细胞）从小鼠和人类RPGN。HB-EGF诱导增加RPGN小鼠EGFR/ErbB 1受体的磷酸化在HB-EGF缺陷小鼠中，肾小球中EGFR活化不存在，RPGN的病程得到改善。体外自分泌HB-EGF诱导足细胞表型转换从小鼠足细胞中有条件地删除Egfr基因可减轻RPGN的严重程度。EGFR的药理学阻断也改善了RPGN的病程，即使在诱导实验性RPGN后4天开始。这表明靶向HB-EGF/EGFR途径也可能有利于治疗人RPGN。
Rapidly progressive glomerulonephritis (RPGN) is a clinical a morphological expression of severe glomerular injury. Glomerular injury manifests as a proliferative histological pattern (“crescents”) with accumulation of T cells and macrophages, and proliferation of intrinsic glomerular cells. We show de novo induction of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in intrinsic glomerular epithelial cells (podocytes) from both mice and humans with RPGN. HB-EGF induction increases phosphorylation of the EGFR/ErbB1 receptor in mice with RPGN. In HB-EGF-deficient mice, EGFR activation in glomeruli is absent and the course of RPGN is improved. Autocrine HB-EGF induces a phenotypic switch in podocytes in vitro. Conditional deletion of the Egfr gene from podocytes of mice alleviates the severity of RPGN. Pharmacological blockade of EGFR also improves the course of RPGN, even when started 4 days after the induction of experimental RPGN. This suggests that targeting the HB-EGF/EGFR pathway could also be beneficial for treatment of human RPGN.