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Published on: April 17, 2013
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PAPP-A as a Potential Target in Thyroid Eye Disease
Cheryl A Conover1, Laurie K Bale1, Marius N Stan1
1Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA.
The Journal of Clinical Endocrinology and Metabolism
|May 16, 2024
Summary
Targeting PAPP-A, an enzyme involved in thyroid eye disease (TED), may offer a new therapeutic approach. Inhibiting PAPP-A reduces IGF-IR signaling, potentially treating proptosis and visual dysfunction in TED patients.
Area of Science:
- Ophthalmology
- Endocrinology
- Molecular Biology
Background:
- Thyroid eye disease (TED) can cause proptosis, leading to disfigurement and vision loss.
- Current treatments for proptosis, like IGF-IR inhibitors, are effective but have side effects.
Purpose of the Study:
- To investigate if PAPP-A inhibitors can selectively reduce IGF-IR signaling in TED.
- To assess the role of PAPP-A in the pathogenesis of TED.
Main Methods:
- TED fibroblasts were cultured and treated with proinflammatory cytokines.
- Fibroblasts were separated into CD34- and CD34+ populations.
- PAPP-A expression, proteolytic activity, and IGF-IR signaling were measured.
Main Results:
- Cytokines increased PAPP-A expression in TED fibroblasts.
- Inhibiting PAPP-A suppressed IGF-IR activation.
- CD34+ fibroblasts were the primary source of PAPP-A and IGF-IR.
Conclusions:
- PAPP-A plays a significant role in TED.
- Targeting PAPP-A offers a potential new therapeutic strategy for TED.
