ArticleFrontiers in cell and developmental biology2026
Connective tissue profiling in keratinized and non-keratinized oral mucosa reveals distinct extracellular and intracellular features.
Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: 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. Methods: Connective tissue samples were harvested and analyzed by transcriptomic sequencing, qPCR, IHC, WB and IF. Results: 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. Discussion: 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.
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