RESUMEN
Drug-induced autoimmunity occurs when exposure to a causative agent leads to serologic or clinical autoimmune responses. Syndromes that may be associated with drug-induced autoimmunity include antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) and drug-induced lupus (DIL). When drug-induced autoimmunity involves the kidney, histological patterns of injury include pauci-immune glomerulonephritis (GN), which occurs with AAV, and immune complex-mediated GN, which is associated with DIL. We present a case of hydralazine-induced dual ANCA-positive vasculitis and nephritis.
RESUMEN
Intu is known as a ciliogenesis and planar polarity effector (CPLANE) protein. Although roles for Intu have been reported during embryonic development and in the context of developmental disorders, its function and regulation in adult tissues remain poorly understood. Here we show that ablation of Intu specifically in kidney proximal tubules aggravates renal ischemia-reperfusion injury, and leads to defective post-injury ciliogenesis. We identify signal transducer and activator of transcription 1 (STAT1) as a novel interacting partner of Intu. In vitro, Intu and STAT1 colocalize at the centriole/basal body area, and Intu promotes proteasomal degradation of STAT1. During cell stress, Intu expression preserves cilia length and cell viability, and these actions are antagonized by STAT1 expression. Thus, we propose a role for Intu in protecting cells and tissues after injury by targeting STAT1 for degradation and maintaining primary cilia.
