Connective tissue profiling in keratinized and non-keratinized oral mucosa reveals distinct extracellular and intracellular features.

Authors

Ruoxuan Huang, Leyao Xu, Chunhsin Hsu, Yuanxiang Liu, Runheng Liu, Shudan Deng, Zhipeng Li, Zetao Chen, Shoucheng Chen, Zhuofan Chen

Published in

Frontiers in cell and developmental biology. Volume 14. Pages 1815527. Epub Jun 12, 2026.

Abstract

Keratinized mucosa is a critical determinant of long-term periodontal and peri-implant tissue stability. Emerging evidence suggests that the underlying connective tissue plays a pivotal role in defining oral mucosal phenotypes. However, the mechanisms by which it shapes the mucosal microenvironment and regulates epithelial keratinization remain incompletely understood. This study aimed to map the molecular blueprints of in situ connective tissue from human keratinized (gingiva, GIN) and non-keratinized (alveolar mucosa, ALV) oral mucosa.
Connective tissue samples were harvested and analyzed by transcriptomic sequencing, qPCR, IHC, WB and IF.
Differential analysis revealed distinct extracellular matrix (ECM) and immune cell composition in their respective microenvironment. GIN was characterized by higher expression level of collagen-related genes, such as COL1 and COL3. Its immune microenvironment was featured by lower proportion of M1 macrophages and notably downregulated complement (C1, C3, C6 and C7) and coagulation cascade. Further analysis of intracellular regulators highlighted reprogrammed metabolism, including retinol metabolism. Downregulated retinoic acid synthesis genes and upregulated catabolic genes indicated depleted retinoic acid in GIN.
In conclusion, GIN and ALV exhibited remarkably different extracellular and intracellular characteristics, in particular ECM, immune microenvironment and metabolism, which in turn provides biomechanical environment for epithelial keratinization. This comprehensive study sheds light on mechanisms regulating mucosal keratinization by connective tissues and lays foundation for therapeutic development in regenerative therapies.

PMID:
42368457
Bibliographic data and abstract were imported from PubMed on 13 Sep 2026.

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