{
  "id": 19718760,
  "title": "A novel pathogenic mechanism of nephrotic syndrome induced by direct stimulation of Ephrin-B1",
  "url": "https://urgent.news/2026/11/12/a-novel-pathogenic-mechanism-of-nephrotic-syndrome-induced-by-direct",
  "topic": "culture",
  "section": "Culture",
  "published": "2026-11-12T22:20:13.000Z",
  "source": {
    "name": "Medical Xpress",
    "slug": "medical-xpress",
    "url": "https://medicalxpress.com/news/2026-11-pathogenic-mechanism-nephrotic-syndrome-ephrin.html"
  },
  "original_language": "en",
  "account": "Researchers from the Department of Cell Biology at Niigata University's Kidney Research Center have uncovered a novel mechanism behind the development of nephrotic syndrome, a kidney disease characterized by excessive protein in the urine. This new insight, published in The American Journal of Pathology, suggests that direct stimulation of the protein Ephrin-B1 can independently trigger podocyte injury, the specialized cells lining the glomerular capillary wall that form a protective barrier against protein leakage into urine.\n\nThe study reveals that Ephrin-B1 stimulation leads to the phosphorylation of both Ephrin-B1 and nephrin, a protein also integral to the slit diaphragm—a crucial barrier against proteinuria. This cascade of events does not require an influx of calcium ions, setting it apart from previously described mechanisms activated by anti-nephrin antibodies.\n\nFurther investigation into the signaling pathways revealed that phosphorylated Ephrin-B1 detaches from nephrin and Par6, another binding protein. Upon release, Par6 interacts with Cdc42, a signaling protein that amplifies its activity. This heightened Cdc42 activity then stimulates calcineurin, a calcium-dependent enzyme, which in turn modulates the regulation of the transcription factor Snail. Reduced Snail expression leads to decreased production of nephrin and Ephrin-B1, exacerbating the glomerular barrier dysfunction.\n\nActivated Cdc42 also independently activates Stat3, a transcription factor that promotes the expression of claudin-1. Increased claudin-1 expression is associated with podocyte dedifferentiation, a state where these cells lose their specialized characteristics and contribute to glomerular injury. The researchers found that while inhibitors targeting calcineurin and angiotensin II type 1 receptor (ARB) could prevent the downregulation of nephrin and Ephrin-B1, they were less effective in halting the rise of claudin-1 expression.\n\nThis novel pathway, where direct Ephrin-B1 stimulation leads to Cdc42 activation and subsequent calcineurin and Stat3 pathway modulation, offers a fresh perspective on the pathogenesis of nephrotic syndrome. The findings suggest that targeting Cdc42 could provide a more effective therapeutic strategy to restore podocyte homeostasis and potentially halt the progression of this debilitating kidney disease.",
  "summary": "A group led by the Department of Cell Biology at the Kidney Research Center, Niigata University, has identified a novel Ca²⁺-independent pathogenic mechanism of nephrotic syndrome. The study is published in The American Journal of Pathology.",
  "key_points": [
    "Direct stimulation of Ephrin-B1 triggers podocyte injury in nephrotic syndrome.",
    "Phosphorylation of Ephrin-B1 and nephrin disrupts the slit diaphragm barrier.",
    "Cdc42 activation amplifies signaling, exacerbating glomerular barrier dysfunction."
  ],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}