RESUMO
Congenital maxillary lateral incisor agenesis (MLIA) is one of the most common subtypes of dental agenesis. Because little is known with regard to the aetiology of this anomaly, the aim of the study was to determine the contribution of nucleotide variants in wingless-type MMTV integration site family, member 10A (WNT10A), msh homeobox 1 (MSX1), and paired box 9 (PAX9) to the risk of MLIA in a Polish population. Coding regions of the selected genes were analysed by direct sequencing in a group of 20 individuals with unilateral and bilateral MLIA, associated or not with other dental anomalies. The frequencies of the identified nucleotide variants were assessed in an additional cohort of patients with isolated dental agenesis (n = 147) and in 178 controls. Mutation screening showed four non-synonymous substitutions located in the highly conserved coding sequence of WNT10A in five (25%) of the 20 patients. Analysis of genotyping results revealed that three of these variants--p.Arg113Cys, p.Phe228Ile, and the newly identified p.Arg171Leu--may represent aetiological mutations underlying MLIA with associated dental anomalies. No mutations that were potentially aetiologic were identified in MSX1 and PAX9. In conclusion, this is the first report implicating coding variants in the WNT10A gene in the aetiology of MLIA. These results will require further confirmation using larger-scale studies.
Assuntos
Anodontia/genética , Variação Genética/genética , Incisivo/anormalidades , Fases de Leitura Aberta/genética , Proteínas Wnt/genética , Adolescente , Adulto , Arginina/genética , Sequência de Bases/genética , Criança , Estudos de Coortes , Sequência Conservada/genética , Cisteína/genética , Feminino , Genótipo , Humanos , Isoleucina/genética , Leucina/genética , Fator de Transcrição MSX1/genética , Masculino , Mutação/genética , Fator de Transcrição PAX9/genética , Fenilalanina/genética , Polimorfismo Genético/genética , Anormalidades Dentárias/genética , Adulto JovemRESUMO
The data showing that butyrate may play an important role in cellular metabolism led us to study its effect on collagen biosynthesis in cultured fibroblasts. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, the effect of butyrate on IGF-I receptor (IGF-IR) expression was evaluated. Confluent human dermal fibroblasts were treated with millimolar concentrations of sodium butyrate (NaB) for 48 hours. It was found that butyrate induced collagen biosynthesis and prolidase activity. It was found that the exposure of the cells to 4 mM butyrate contributed to a distinct increase in IGF-IR. It was accompanied by a parallel increase in the expression of SOS protein and MAP-kinases (ERK1, ERK2). It was found that the MEK inhibitor decreased collagen biosynthesis and expression of MAP-kinases (ERK1, ERK2), while NaB counteracted the process. The data suggest that butyrate-dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling.
Assuntos
Butiratos/farmacologia , Colágeno/biossíntese , Fibroblastos/metabolismo , Western Blotting , Sobrevivência Celular , Células Cultivadas , Dipeptidases/química , Eletroforese em Gel de Poliacrilamida , Fibroblastos/efeitos dos fármacos , Humanos , Indicadores e Reagentes , Proteína Quinase 1 Ativada por Mitógeno/química , Receptor IGF Tipo 1/efeitos dos fármacos , Proteína Son Of Sevenless de Drosófila/químicaRESUMO
The data showing that butyrate may play an important role in cellular metabolism led us to study its effect on collagen biosynthesis in cultured fibroblasts. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, the effect of butyrate on IGF-I receptor (IGF-IR) expression was evaluated. Confluent human dermal fibroblasts were treated with millimolar concentrations of sodium butyrate (NaB) for 48 hours. It was found that butyrate induced collagen biosynthesis and prolidase activity. It was found that the exposure of the cells to 4 mM butyrate contributed to a distinct increase in IGF-IR. It was accompanied by a parallel increase in the expression of Sos protein and MAP-kinases (ERK1, ERK2). It was found that the MEK inhibitor decreased collagen biosynthesis and expression of MAP-kinases (ERK1, ERK2), while NaB counteracted the process. The data suggests that butyrate-dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling.
Assuntos
Butiratos/farmacologia , Colágeno/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Receptor IGF Tipo 1/metabolismo , Butiratos/administração & dosagem , Células Cultivadas , Colágeno/biossíntese , Dipeptidases/efeitos dos fármacos , Dipeptidases/metabolismo , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/genética , Receptor IGF Tipo 1/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Proteína Son Of Sevenless de Drosófila/genéticaRESUMO
UNLABELLED: The role of neuroendocrine cells (NC) in physiology and pathology of the human's respiratory tract is not fully understood. The aim of the study was the quantitative and morphometric assessment of NC in nasal mucosa in some pathological states. PATIENTS AND METHOD: 40 patients, aged 28-63 years, with clinical signs of chronic, hypertrophic rhinosinusitis were qualified for the study. Rhinitis chronica hypertrophica coexisted with aspirin triad or asthma in 10 patients (group I), with advanced obstructive sleep apnea syndrome (OSAS) in 10 patients (respiratory disturbance index, RDI>40, group II). Group III consisted of 10 patients with simple rhinitis chronica hypertrophica who habitually smoked cigarettes (at least 20 cigarettes a day) while 10 non-smoking patients with simple rhinitis chronica hypertrophica were qualified to the control group. Fragments of nasal mucosa of approximately 0.5 cm(2) were collected from medial or inferior turbinate during mucoplasty procedures. NC were detected immunohistochemically using antibodies against chromogranin A (DAKO). The microscopic sections were evaluated in the light microscopy. RESULTS: The study did not reveal the increased number of NC in examined fragments of nasal mucosa. Scattered NC were detected in single preparations of nasal mucous membrane in some patients in all groups. The number of detected neuroendocrine cells did not differ statistically between groups.
