biostudies-literatureUnknown13Liu LHemoporfin-mediated photodynamic therapy (HMME-PDT) has demonstrated significant advantages in the treatment of Port-wine stains (PWSs). However, the therapeutic efficacy of HMME-PDT remains suboptimal in a subset of patients. Somatic mosaic mutations in <i>GNAQ</i> (c.548G>A, p. R183Q) are frequently detected in endothelial cells (ECs) of lesions and represent a common pathogenic mechanism. In this study, we successfully established an <i>in vitro</i> model of PWSs by introducing the <i>GNAQ</i> p. R183Q mutation into HUVECs using lentiviral infection. Our results revealed that <i>GNAQ</i> p. R183Q mutation enhanced ECs proliferation, migration, and angiogenesis. Moreover, the mutation augmented anti-apoptotic mechanisms, thereby conferring heightened resistance to HMME-PDT-induced apoptoFrontiers in cell and developmental biology1622961https://www.ebi.ac.uk/biostudies/studies/S-EPMC12411732biostudies-literatureEndothelial &lt;i&gt;GNAQ&lt;/i&gt; p.R183Q mutation confers hemoporfin-mediated photodynamic therapy resistance and drives pathological angiogenesis via the angiopoietin-2/TIE2/PI3K/AKT pathway.PMC12411732Liu HLiu YHu FLiu LLuo JXie LYu JXu HWang LfalseEndothelial &lt;i&gt;GNAQ&lt;/i&gt; p.R183Q mutation confers hemoporfin-mediated photodynamic therapy resistance and drives pathological angiogenesis via the angiopoietin-2/TIE2/PI3K/AKT pathway.Hemoporfin-mediated photodynamic therapy (HMME-PDT) has demonstrated significant advantages in the treatment of Port-wine stains (PWSs). However, the therapeutic efficacy of HMME-PDT remains suboptimal in a subset of patients. Somatic mosaic mutations in <i>GNAQ</i> (c.548G>A, p. R183Q) are frequently detected in endothelial cells (ECs) of lesions and represent a common pathogenic mechanism. In this study, we successfully established an <i>in vitro</i> model of PWSs by introducing the <i>GNAQ</i> p. R183Q mutation into HUVECs using lentiviral infection. Our results revealed that <i>GNAQ</i> p. R183Q mutation enhanced ECs proliferation, migration, and angiogenesis. Moreover, the mutation augmented anti-apoptotic mechanisms, thereby conferring heightened resistance to HMME-PDT-induced apopto2025-01-01T00:00:00Z20252026-06-03T06:59:09.106Z2026-05-29T03:05:41.844ZS-EPMC124117324091774710.3389/fcell.2025.1622961