Related Experiment Video
Updated: May 28, 2026
12:37
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Hmga2-dependent cAMP signaling drives UVB-induced melanocyte stem cell activation
Leanne R Donahue1, Chia-Hsin Hsu1, Youngeun H Yang1
1Department of Biomedical and Translational Sciences, Cornell University, Ithaca, New York, USA.
The Journal of Investigative Dermatology
|May 26, 2026
Summary
High mobility group AT-hook 2 (Hmga2) regulates skin damage responses after ultraviolet-B (UVB) irradiation by controlling cyclic-AMP (cAMP) levels. Loss of Hmga2 prevents epidermal hyperplasia and stem cell migration, highlighting a key molecular pathway.
Area of Science:
- Dermatology
- Molecular Biology
- Stem Cell Biology
Background:
- Ultraviolet-B (UVB) irradiation triggers skin damage responses, including epidermal hyperplasia and immune cell infiltration.
- Follicular melanocyte stem cells (McSCs) migrate to the interfollicular epidermis following UVB exposure.
- The oncofetal protein High mobility group AT-hook 2 (Hmga2) is implicated in cellular processes, but its role in UVB-induced skin responses is unclear.
Purpose of the Study:
- To investigate the role of Hmga2 in regulating UVB-induced epidermal damage and McSC migration.
- To elucidate the molecular mechanisms, particularly the cyclic-AMP (cAMP) pathway, by which Hmga2 influences these responses.
Main Methods:
- Utilized mouse models with Hmga2 loss-of-function (Hmga2-/-) and wild-type littermates.
- Exposed skin to UVB irradiation and analyzed epidermal hyperplasia, immune cell infiltration (neutrophils), and McSC migration.
- Performed RNA sequencing (RNAseq) on keratinocytes to identify gene expression changes.
- Administered forskolin, a cAMP pathway activator, to Hmga2-/- mice.
Main Results:
- Somatic expression of Hmga2 was identified in the basal layer of hyperplastic UVB-exposed keratinocytes.
- Loss of Hmga2 significantly reduced epidermal hyperplasia, neutrophil infiltration, and McSC migration to the interfollicular epidermis.
- RNAseq revealed increased expression of Adenosine A1 receptor (Adora1), a negative regulator of cAMP, in Hmga2-deficient keratinocytes.
- Forskolin administration rescued McSC migration in Hmga2-/- mice, indicating the involvement of the cAMP pathway.
Conclusions:
- Hmga2 acts as a crucial regulator of the cutaneous response to UVB irradiation.
- The Hmga2-cAMP axis is a key pathway controlling UVB-induced epidermal hyperplasia and McSC migration.
- Targeting the Hmga2-cAMP pathway may offer therapeutic strategies for managing skin damage from UVB exposure.
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