{
  "id": 9754025,
  "title": "Calcium dysregulation amplifies fibrotic responses to TGFβ in human Friedreich's ataxia fibroblasts",
  "url": "https://urgent.news/2026/09/25/calcium-dysregulation-amplifies-fibrotic-responses-to-tgf-in-human",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-25T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753166v1?rss=1"
  },
  "original_language": "en",
  "account": "Friedreich's ataxia (FA) is a genetic disorder resulting from the absence of a protein called frataxin (FXN). This condition leads to the degeneration of nerves and can cause heart problems, as the heart wall becomes stiffened due to a process called fibrosis. However, the exact mechanisms behind fibrosis in FA have not been thoroughly understood.\n\nResearchers have now explored the role of calcium (Ca) in the development of fibrosis in FA patient-derived fibroblasts. They discovered that FA fibroblasts had an early predisposition to fibrosis, along with higher expression of genes regulated by a calcium-responsive protein called NFAT.\n\nWhen these fibroblasts transformed into myofibroblasts (a key step in fibrosis), they showed a more intense activation of pro-fibrotic genes (such as CCN2 and NOX4) and a decrease in anti-fibrotic genes (like CCN3). Interestingly, these changes in gene expression were linked to the amount of residual FXN in the fibroblasts. FA fibroblasts also displayed higher cytosolic calcium levels and reduced expression of a protein called Na-Ca exchanger (NCX1), which is directly related to the amount of FXN present. Moreover, inhibiting NCX1 in normal fibroblasts caused them to exhibit similar calcium profiles and fibrosis patterns as FA fibroblasts. However, when NCX1 was reintroduced into FA fibroblasts, their calcium levels stabilized, and the fibrosis-promoting gene CCN2 was reduced.\n\nThese findings suggest that NCX1 plays a crucial role in regulating fibrotic changes in FA. Additionally, the study indicates that calcium imbalance within FA fibroblasts could be an intrinsic factor contributing to fibrosis, which may potentially be targeted for therapeutic intervention.",
  "summary": "Friedreich's ataxia (FA) is an inherited disease caused by loss of frataxin (FXN) and characterized by neurodegeneration and fatal cardiomyopathy. Cardiac fibrosis contributes to cardiomyopathy by stiffening the heart wall, yet the underlying mechanisms remain unknown. Here, we investigated pro-fibrotic predisposition in FA patient-derived fibroblasts, focusing on the role of cytosolic calcium…",
  "key_points": [],
  "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."
}