{
  "id": 10406860,
  "title": "PDLIM5 Modulates YAP1 Localisation and Fibrogenic Gene Expression in Hepatic Stellate Cells",
  "url": "https://urgent.news/2026/09/28/pdlim5-modulates-yap1-localisation-and-fibrogenic-gene-expression-in",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-28T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.748507v1?rss=1"
  },
  "original_language": "en",
  "account": "Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis. Upon liver injury and chronic inflammation, HSCs transform into an activated state and produce fibrotic extracellular matrix (ECM) components, such as collagen 1. The ECM influences HSC activation through mechanical cues involving integrins and a transcription factor called YAP1. However, how these external mechanical signals lead to a molecular response that modifies YAP1's nuclear localization remains unclear.\n\nResearch has shown that the protein PDLIM5, which contains PDZ and LIM domains, may influence YAP1's shuttling in human epithelial cells. This study aimed to determine if PDLIM5 is expressed in HSCs and if it contributes to YAP1-associated HSC mechano-activation. The results indicate that PDLIM5 protein is present in HSCs within fibrotic human and mouse liver tissue. Moreover, PDLIM5 mRNA and protein were detected in primary human and mouse HSCs, as well as in the immortalized HSC LX-2 cell line.\n\nFurthermore, PDLIM5 was found to localize with actin stress fibers, suggesting its involvement in HSC adhesion. Co-immunoprecipitation and proximity ligation assays in LX-2 cells revealed an association between PDLIM5 and YAP1. To investigate the impact of PDLIM5 inhibition on YAP1 nuclear localization and fibrotic gene expression, pharmacological (using paclitaxel) and genetic (using siRNA and CRISPR interference) methods were employed in HSCs. The findings demonstrate that inhibiting PDLIM5 leads to reduced YAP1 nuclear localization and decreased expression of fibrotic genes, specifically COL1A1 and ACTA2, in LX-2 cells.\n\nIn summary, these results support the notion that PDLIM5 plays a regulatory role in modulating YAP1 localization and fibrogenic gene expression in HSCs.",
  "summary": "Hepatic stellate cells (HSCs) are the key cellular drivers of liver fibrosis. During liver injury and chronic inflammation HSCs adopt an activated phenotype and secrete fibrotic extracellular matrix (ECM) components such as collagen 1. Mechanical cues derived from the fibrotic ECM drive and support the activation of HSCs, via mechanisms that involve integrins and the mechano-sensitive…",
  "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."
}