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Updated: Jun 13, 2025
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Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
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Connexin Hemichannel Inhibition and Human Genodermatoses.
Fabio Mammano1, Amy S Paller2, Thomas W White3
1Institute of Biochemistry and Cell Biology, Italian National Research Council, Rome, Italy; Department of Physics and Astronomy "G. Galilei", University of Padova, Padova, Italy.
The Journal of Investigative Dermatology
|September 13, 2024
Summary
Pathogenic variants in connexin genes elevate hemichannel activity, causing skin diseases like KID syndrome and hidrotic ectodermal dysplasia (HED). Inhibiting this activity offers a promising therapeutic strategy for these conditions.
Area of Science:
- Genetics
- Dermatology
- Biophysics
Background:
- Pathogenic variants in connexin genes cause rare genetic skin disorders.
- These disorders, including keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (HED), are characterized by increased hemichannel activity.
- Understanding the biophysical mechanisms of variant connexins is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of increased hemichannel activity in connexin-related skin diseases.
- To evaluate the therapeutic potential of inhibiting aberrant hemichannel function.
- To explore applications for other genetic skin conditions involving elevated hemichannel activity.
Main Methods:
- Biophysical studies of variant connexins to elucidate disease mechanisms.
- Pharmacological inhibition of hemichannel activity.
- Utilizing engineered monoclonal antibodies (mAbs) in mouse models of HED and KID.
Main Results:
- Pathogenic variants in connexin genes lead to heightened hemichannel activity.
- Inhibition of this acquired hemichannel activity demonstrated potential to alleviate epidermal pathology in mouse models.
- Pharmacological blockers and mAbs effectively targeted hemichannel function.
Conclusions:
- Inhibiting elevated hemichannel activity is a viable therapeutic strategy for KID syndrome and HED.
- This approach holds promise for treating other connexin-based genetic skin diseases.
- Further research into connexin hemichannel modulation could lead to novel treatments.
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