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Updated: Jan 8, 2026
Author Spotlight: Unlocking the Mysteries of Oral Potential Malignancies
Published on: August 11, 2023
Non-Syndromic Hereditary Gingival Fibromatosis Driven by Chymase Deficiency Is Attenuated by Verteporfin-Loaded
Xin Chen1, Yuqing Guo1, Yangqiao Qing1
1Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Aim:
To identify novel non-syndromic hereditary gingival fibromatosis (nsHGF)-associated pathogenic variants and discover therapeutic targets for innovative, minimally invasive therapies.
Materials And Methods:
Whole-genome sequencing was performed to identify the pathogenic variant in a family with nsHGF. Levels of fibrosis markers and the yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) in gingival fibroblasts were measured by qPCR, western blot and immunofluorescence. Conditioned medium from gingival fibroblasts was used to treat THP-1-derived macrophages. In vivo pro-fibrotic behaviour of CHYMASE-silenced gingival fibroblasts and verteporfin-loaded exosome efficacy were evaluated in NOD/SCID mice.
Results:
We identified a novel CHYMASE (CMA1) nonsense mutation (c.114C>A, p.Tyr38*) in the nsHGF family. This mutation caused chymase deficiency in the patient's gingival fibroblasts, directly leading to extracellular matrix (ECM) overproduction through YAP/TAZ activation. Moreover, CHYMASE-silenced gingival fibroblasts promoted interleukin-6 (IL-6) secretion by macrophages, thereby amplifying pro-fibrotic responses in gingival fibroblasts. The YAP inhibitor verteporfin suppressed ECM overproduction in CHYMASE-silenced gingival fibroblasts. In vivo, topical administration of verteporfin-loaded exosomes significantly attenuated chymase deficiency-induced fibrosis.
Conclusion:
Our findings support the pathogenic role of the CHYMASE mutation in nsHGF, establish chymase deficiency and consequent YAP/TAZ activation as the underlying mechanism and propose verteporfin-loaded exosomes as a promising therapeutic strategy for nsHGF-associated gingival overgrowth.
