Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture

Toxicology
Lorella MarinucciEleonora Lumare

Abstract

Prenatal exposure to diazepam, a prototype sedative drug that belongs to Benzodiazepines, can lead to orofacial clefting in human newborns. By using real-time PCR, in the present study we investigated whether diazepam elicits gene expression alterations in extracellular matrix (ECM) components, growth factors and gamma-aminobutyric acid receptor (GABRB3), implicated in the coordinate regulation of palate development. Palate fibroblasts were treated with diazepam (Dz-N fibroblasts) and compared to cleft lip-palate (CLP) fibroblasts obtained from patients with no known exposure to diazepam or other teratogens. Untreated fibroblasts from non-CLP patients were used as control. The results showed significant convergences in gene expression pattern of collagens, fibromodulin, vitronectin, tenascin C, integrins and metalloprotease MMP13 between Dz-N and CLP fibroblasts. Among the growth factors, constitutive Fibroblast Growth Factor 2 (FGF2) was greatly enhanced in Dz-N and CLP fibroblasts and associated with a higher reduction of FGF receptor. Transforming Growth Factor beta 3 (TGFbeta(3)) resulted up-regulated in CLP fibroblasts and decreased in Dz-N fibroblasts. We found phenotypic differences exhibited by Dz-N and CLP fibroblasts ...Continue Reading

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Citations

Jul 22, 2014·Birth Defects Research. Part A, Clinical and Molecular Teratology·Adrianna MostowskaPaweł P Jagodziński
Jun 19, 2013·PloS One·Gerson Shigeru KobayashiMaria Rita Passos-Bueno
Nov 14, 2019·International Journal of Molecular Sciences·Chiara ArgentatiSabata Martino
Dec 2, 2020·Dental Materials : Official Publication of the Academy of Dental Materials·Stefano PaganoLorella Marinucci

Related Concepts

GABRB3 protein, human
Cleft Lip
Cleft Palate, Isolated
Valium
Fibroblasts
GABA-A Receptor gamma Subunit
Poly(A) Tail
Anti-Anxiety Effect
Nested Case-Control Studies
Extracellular Matrix Proteins

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