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Smad3 Suppresses Epithelial Cell Migration and Proliferation via the Clock Gene Dec1, Which Negatively Regulates the Expression of Clock Genes Dec2 and Per1
Smad3 Limits Epithelial Cell Movement and Growth Through the Clock Gene Dec1, Which Reduces Other Clock Gene Activity
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Abstract
Smad3 knockout mice exhibited a decreased locomotor activity amplitude and reduced Dec1 expression in multiple tissues.
- Dec1 expression decreased in the suprachiasmatic nucleus, liver, kidney, and tongue of Smad3 knockout mice.
- Increased expression of Dec2 and Per1 was observed in Smad3 knockout mice compared to controls.
- Immunohistochemical analysis showed decreased Dec1 and increased Dec2 and Per1 expression in the endothelial cells of the kidney and liver in Smad3 knockout mice.
- Smad3 overexpression in NIH3T3 cells increased Dec1 expression while decreasing Dec2 and Per1 expression.
- In a wound-healing experiment, reduced Dec1 expression in Smad3 knockout mice accelerated mucosal wound healing.
- Dec1 overexpression reduced E-cadherin and proliferating cell nuclear antigen expression, while Dec2 overexpression had the opposite effect.
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