ArticleMolecular medicine (Cambridge, Mass.)
Retinoic acid, GABA-ergic, and TGF-beta signaling systems are involved in human cleft palate fibroblast phenotype.
Article in Molecular medicine (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 41 citations in OpenAlex.
- Functional variant at 19q13.3 confers nonsyndromic cleft palate susceptibility by regulatingiScience · 2025Article
- E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner.Cell communication and signaling : CCS · 2024Article
- An improved multicellular human organoid model for the study of chemical effects on palatal fusion.Birth defects research · 2023Article
- Genetic Factors in Nonsyndromic Orofacial Clefts.Global medical genetics · 2020Review
- Article
- Analysis of dermal fibroblasts isolated from neonatal and child cleft lip and adult skin: Developmental implications on reconstructive surgery.International journal of molecular medicine · 2017Article
- A novel de novo mutation in MYT1, the unique OAVS gene identified so far.European journal of human genetics : EJHG · 2017Article
- Palate morphogenesis: current understanding and future directions.Birth defects research. Part C, Embryo today : reviews · 2010Review
- Oral facial clefts and gene polymorphisms in metabolism of folate/one-carbon and vitamin A: a pathway-wide association study.Genetic epidemiology · 2009Article
- Effects of bisphenol-A and other endocrine disruptors compared with abnormalities of schizophrenia: an endocrine-disruption theory of schizophrenia.Schizophrenia bulletin · 2009Review
- Alteration of medial-edge epithelium cell adhesion in two Tgf-beta3 null mouse strains.Differentiation; research in biological diversity · 2008Article
- Cleft palate only: current concepts.ORAL & implantologyArticle
- New insights in orofacial cleft: epidemiological and genetic studies on italian samples.ORAL & implantologyArticle
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During embryogenesis, a complex interplay between extracellular matrix (ECM) molecules, regulatory molecules, and growth factors mediates morphogenetic processes involved in palatogenesis. Transforming growth factor-beta (TGF-beta), retinoic acid (RA), and gamma-aminobutyric acid (GABA)ergic signaling systems are also potentially involved. Using [3H]glucosamine and [35S]methionine incorporation, anion exchange chromatography, semiquantitative radioactive RT-PCR, and a TGF-beta binding assay, we aimed to verify the presence of phenotypic differences between primary cultures of secondary palate (SP) fibroblasts from 2-year-old subjects with familial nonsyndromic cleft lip and/or palate (CLP-SP fibroblasts) and age-matched normal SP (N-SP) fibroblasts. The effects of RA--which, at pharmacologic doses, induces cleft palate in newborns of many species--were also studied. We found an altered ECM production in CLP-SP fibroblasts that synthesized and secreted more glycosaminoglycans (GAGs) and fibronectin (FN) compared with N-SP cells. In CLP-SP cells, TGF-beta3 mRNA expression and TGF-beta receptor number were higher and RA receptor-alpha (RARA) gene expression was increased. Moreover, we demonstrated for the first time that GABA receptor (GABRB3) mRNA expression was upregulated in human CLP-SP fibroblasts. In N-SP and CLP-SP fibroblasts, RA decreased GAG and FN secretion and increased TGF-beta3 mRNA expression but reduced the number of TGF-beta receptors. TGF-beta receptor type I mRNA expression was decreased, TGF-beta receptor type II was increased, and TGF-beta receptor type III was not affected. RA treatment increased RARA gene expression in both cell populations but upregulated GABRB3 mRNA expression only in N-SP cells. These results show that CLP-SP fibroblasts compared with N-SP fibroblasts exhibit an abnormal phenotype in vitro and respond differently to RA treatment, and suggest that altered crosstalk between RA, GABAergic, and TGF-beta signaling systems could be involved in human cleft palate fibroblast phenotype.
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