Smad3 suppresses epithelial cell migration and proliferation via the clock gene Dec1, which negatively regulates the expression of clock genes Dec2 and Per1.

Smad3 suppresses epithelial cell migration and proliferation via the clock gene Dec1, which negatively regulates the expression of clock genes Dec2 and Per1. Am J Pathol. 2019 Jan 18;: Authors: Sato F, Otsuka T, Kohsaka A, Le HT, Bhawal UK, Muragaki Y Abstract Smad3 has circadian expression; however, whether Smad3 affects the expression of clock genes is poorly understood. Here, we investigated the regulatory mechanisms between Smad3 and the clock genes Dec1, Dec2, and Per1. In Smad3 knockout mice, the amplitude of locomotor activity was decreased and Dec1 expression was decreased in the suprachiasmatic nucleus, liver, kidney, and tongue compared with control mice. Conversely, Dec2 and Per1 expression was increased compared with that of control mice. In Smad3 knockout mice, immunohistochemical staining revealed that Dec1 expression decreased, whereas Dec2 and Per1 expression increased in the endothelial cells of the kidney and liver. In NIH3T3 cells, Smad3 overexpression increased Dec1 expression, but decreased Dec2 and Per1 expression. In a wound-healing experiment using Smad3 knockout mice, Dec1 expression decreased in the basal cells of squamous epithelium, promoting wound healing of the mucosa. Finally, the migration and proliferation of Smad3 knockdown squamous carcinoma cells was suppressed by Dec1 overexpression, but promoted by Dec2 overexpression. Dec1 overexpression decreased E-cadherin and proliferating cell nuclear antige...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research