The GATA family proteins are a group of zinc finger transcription factors that are expressed in human and mammalian animals and play an important role in mammalian organ morphogenesis, cell proliferation and sex differentiation. GATA-4 and GATA-6 have been identified in the ovaries and testes of humans, mice, pigs and chickens. GATA-4 contributes to fetal male gonadal development by regulating the genes that mediate Müllerian duct regression and the onset of testosterone production. GATA-4 and GATA-6 are localized in and regulate the function of the ovarian and testicular somatic cells of fetal mice, especially granulosa cells, thecal cells, Sertoli cells and Leydig cells. GATA-4 is also present in the germ cells of fetal and prepubertal mice.
Animals ; Chickens ; Female ; GATA4 Transcription Factor ; metabolism ; GATA6 Transcription Factor ; metabolism ; Humans ; Male ; Mice ; Ovary ; embryology ; Reproduction ; Swine ; Testis ; embryology ; Transcription Factors ; classification

OBJECTIVE: To investigate the expression of Dickkopf-1 and GATA-6 in laryngeal carcinoma and to discuss their relevance and the roles in carcinogenesis and development of laryngeal carcinoma. METHOD: Immunohistochemical technique was used to detect the expression of Dickkopf-1 and GATA-6 protein in 48 tissues of larynge al carcinoma, 48 para-carcinoma tissues and 20 normal laryngeal mucosal tissues. RESULT: (1) The expression of Dick kopf-1 protein in laryngeal cancer is significantly lower than in para-carcinoma tissues and normal laryngeal mucosa tissues (P < 0.05). (2) The expression of GATA-6 protein in laryngeal cancer is significantly higher than in para-carcinoma tissues and normal laryngeal mucosa tissues (P < 0.05). (3) The expression of Dickkopf-1 and GATA-6 protein in laryngeal cancer is correlated with lymph node metastasis, clinical stage, histological grade (P < 0.05). (4) The expression of Dickkopf-1 and GATA-6 are negatively correlated in laryngeal cancer. CONCLUSION The expression of Dickkopf-1 and GATA-6 may contribute to the carcinogenesis and development of laryngeal carcinoma.
Adult ; Aged ; Female ; GATA6 Transcription Factor ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30^th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m² (P₁₀-P₁₅)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.
Male ; Child ; Humans ; Child, Preschool ; Infant ; Diabetes Mellitus, Type 2/complications* ; Mutation, Missense ; C-Peptide/genetics* ; China ; Insulin/genetics* ; Glucose ; Blood Glucose ; GATA6 Transcription Factor/genetics*

Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; GATA6 Transcription Factor ; genetics ; Gene Expression Regulation ; Muscle, Smooth, Vascular ; drug effects ; Myocytes, Smooth Muscle ; drug effects ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology

OBJECTIVETo study the role of sirtuin 1 (SIRT1) in Fas ligand (FasL) expression regulation during vascular lesion formation and to elucidate the potential mechanisms.

METHODSSIRT1 and FasL protein levels were detected by Western blotting in either mouse arteries extract or the whole rat aortic vascular smooth muscle cell (VSMC) lysate. Smooth muscle cell (SMC)-specific human SIRT1 transgenic (Tg) C57BL/6 mice and their littermate wild-type (WT) controls underwent complete carotid artery ligation (ligation groups) or the ligation-excluded operation (sham groups). The carotid arteries were collected 1 day after operation. Reverse transcription-polymerase chain reaction was performed to detect the mRNA levels of SIRT1 and FasL. Luciferase reporter assays were performed to detect the effect of WT-SIRT1, a dominant-negative form of SIRT1 (SIRT1H363Y), and GATA-6 on the promoter activity of FasL. Flow cytometry assay was applied to measure the hypodiploid DNA content of VSMC so as to monitor cellular apoptosis.

RESULTSSIRT1 was expressed in both rat aortic VSMCs and mouse arteries. Forced SIRT1 expression increased FasL expression both in injured mouse carotid arteries 1 day after ligation (P<0.001) and VSMCs treated with serum (P<0.05 at the transcriptional level, P<0.001 at the protein level). No notable apoptosis was observed. Furthermore, transcription factor GATA-6 increased the promoter activity of FasL (P<0.001). The induction of FasL promoter activity by GATA-6 was enhanced by WT-SIRT1 (P<0.001), while SIRT1H363Y significantly relieved the enhancing effect of WT-SIRT1 on GATA-6 (P<0.001).

CONCLUSIONSOverexpression of SIRT1 up-regulates FasL expression in both flow-restricted mouse carotid arteries and serum-stimulated VSMCs. The transcription factor GATA-6 participates in the transcriptional regulation of FasL expression by SIRT1.

Animals ; Apoptosis ; Carotid Arteries ; physiology ; Fas Ligand Protein ; genetics ; GATA6 Transcription Factor ; physiology ; Male ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Myocytes, Smooth Muscle ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1 ; physiology ; Up-Regulation