PDF(Pubmed)
Abstract：
UNASSIGNED: During glomerular diseases, podocyte-specific pathways can modulate the intensity of histological disease and prognosis. The therapeutic targeting of these pathways could thus improve the management and prognosis of kidney diseases. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway, classically described in immune cells, has been recently described in detail in intrinsic kidney cells.
UNASSIGNED: We describe STAT5 expression in human kidney biopsies from patients with focal segmental glomerulosclerosis (FSGS) and studied mice with a podocyte-specific Stat5 deletion in experimental glomerular diseases.
UNASSIGNED: Here, we show, for the first time, that STAT5 is activated in human podocytes in FSGS. In addition, podocyte-specific Stat5 inactivation aggravates the structural and functional alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of autophagic flux. Finally, interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes, and its administration alleviates glomerular injury in vivo by maintaining autophagic flux in podocytes.
UNASSIGNED: Activating podocyte STAT5 with commercially available IL-15 represents a potential new therapeutic avenue for FSGS.
UNASSIGNED: We describe STAT5 expression in human kidney biopsies from patients with focal segmental glomerulosclerosis (FSGS) and studied mice with a podocyte-specific Stat5 deletion in experimental glomerular diseases.
UNASSIGNED: Here, we show, for the first time, that STAT5 is activated in human podocytes in FSGS. In addition, podocyte-specific Stat5 inactivation aggravates the structural and functional alterations in a mouse model of FSGS. This could be due, at least in part, to an inhibition of autophagic flux. Finally, interleukin 15 (IL-15), a classical activator of STAT5 in immune cells, increases STAT5 phosphorylation in human podocytes, and its administration alleviates glomerular injury in vivo by maintaining autophagic flux in podocytes.
UNASSIGNED: Activating podocyte STAT5 with commercially available IL-15 represents a potential new therapeutic avenue for FSGS.
摘要：
■在肾小球疾病期间，足细胞特异性通路可以调节组织学疾病的强度和预后。因此，这些途径的治疗靶向可以改善肾脏疾病的管理和预后。Janus激酶/信号转导和转录激活因子(JAK/STAT)通路,在免疫细胞中经典描述，最近在内在肾细胞中进行了详细描述。
■我们描述了来自局灶性节段肾小球硬化（FSGS）患者的人肾活检中STAT5的表达，并研究了实验性肾小球疾病中足细胞特异性Stat5缺失的小鼠。
■这里，我们展示，第一次,STAT5在FSGS的人足细胞中被激活。此外,足细胞特异性Stat5失活加重了FSGS小鼠模型的结构和功能改变。这可能是由于,至少在某种程度上,抑制自噬通量。最后,白细胞介素15（IL-15），免疫细胞中STAT5的经典激活剂，增加人足细胞中的STAT5磷酸化，其给药通过维持足细胞的自噬通量减轻体内肾小球损伤。
用市售IL-15激活足细胞STAT5代表了FSGS的潜在新治疗途径。
■我们描述了来自局灶性节段肾小球硬化（FSGS）患者的人肾活检中STAT5的表达，并研究了实验性肾小球疾病中足细胞特异性Stat5缺失的小鼠。
■这里，我们展示，第一次,STAT5在FSGS的人足细胞中被激活。此外,足细胞特异性Stat5失活加重了FSGS小鼠模型的结构和功能改变。这可能是由于,至少在某种程度上,抑制自噬通量。最后,白细胞介素15（IL-15），免疫细胞中STAT5的经典激活剂，增加人足细胞中的STAT5磷酸化，其给药通过维持足细胞的自噬通量减轻体内肾小球损伤。
用市售IL-15激活足细胞STAT5代表了FSGS的潜在新治疗途径。
