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.
■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。