TGF-β-Dependent α11 Integrin Expression Is Reduced in Aging Gingival Wounds
Summary: This study investigates how aging disrupts TGF-β-mediated regulation of α11 integrin—a key collagen receptor essential for fibroblast function and extracellular matrix remodeling—in gingival wound healing. Primary human gingival fibroblasts from young and aged donors showed significantly lower baseline α11 integrin (76% less mRNA, 33% less protein), TGF-β1 (34% less mRNA, 40% less protein), and overall TGF-β activity (38% reduction) in older cells. Exogenous TGF-β1 treatment upregulated α11 integrin mRNA (3.6-fold) and protein (45%) in young fibroblasts but had no effect in aged ones, indicating blunted responsiveness. In vivo, gingival wounds in aged mice exhibited reduced collagen deposition (61%), poorer collagen alignment (48%), lower α11 integrin (77%), and TGF-β1 (86%) compared to young mice. Findings identify diminished TGF-β1 expression and signaling as a key mechanism driving reduced α11 integrin in aging, contributing to impaired connective tissue repair and delayed healing in oral/gingival wounds. Highlights potential therapeutic targets (e.g., TGF-β pathway modulation) to improve wound outcomes in older populations.
Key Highlights:
- Human fibroblasts (aged vs. young): ↓ α11 integrin (mRNA -76%, protein -33%), ↓ TGF-β1 (mRNA -34%, protein -40%), ↓ TGF-β activity (-38%).
- TGF-β1 stimulation: Strong α11 upregulation in young cells (mRNA +3.6×, protein +45%); no response in aged cells.
- In vivo (aged mice wounds): ↓ collagen deposition (-61%), ↓ collagen organization (-48%), ↓ α11 integrin (-77%), ↓ TGF-β1 (-86%).
- Mechanism: Aging impairs TGF-β1-dependent α11 integrin signaling → reduced fibroblast-collagen interaction → poor matrix remodeling/healing.
- Relevance: Explains age-related delays in oral/gingival wound repair; extends to broader aging wound healing deficits (e.g., skin, chronic ulcers); suggests pathway restoration as strategy for elderly patients.
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Keywords: α11 integrin, TGF-β1, aging wound healing, gingival wounds, collagen remodeling, aged fibroblasts