Down-regulation of SHH/BMP4 signalling in human anorectal malformations. 2009

J Zhang, and Z B Zhang, and H Gao, and D Zhang, and W L Wang
Department of Paediatric Surgery, Shengjing Hospital, China Medical University, Shenyang, China.

The sonic hedgehog homologue (SHH)/bone morphogenetic protein 4 (BMP4) signalling pathway is involved in the morphogenesis of many organ systems. This study was designed to investigate the expression of SHH/BMP4 pathway components in human anorectal malformations (ARMs) and the relationship between expression of their genes and the occurrence of ARMs. Expression of SHH, GLI family zinc finger 2 (GLI2) and BMP4 mRNA in the posterior wall of the terminal rectum in 40 patients with ARMs (15 high-type and 25 low-type) and 10 normal controls was assessed by reverse transcription-polymerase chain reaction. Levels of SHH, GLI2 and BMP4 proteins were assessed by immunohistochemistry and Western blotting. The expressions of SHH, GLI2 and BMP4 were significantly lower in patients with high-type compared with those with low-type anomalies and controls. Patients with low-type ARMs differed from controls only in the expression of GLI2 mRNA. It is concluded that down-regulation of the SHH/BMP4 signalling pathway may be related to the occurrence of high-type ARMs, but the mechanism responsible for low-type ARMs remains unclear.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D012007 Rectum The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL. Rectums
D004065 Digestive System Abnormalities Congenital structural abnormalities of the DIGESTIVE SYSTEM. Abnormalities, Digestive System,Abnormality, Digestive System,Digestive System Abnormality
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075746 Zinc Finger Protein Gli2 A transcriptional activator that contains five adjacent CYS2-HIS2 ZINC FINGERS. It functions in the hedgehog signaling pathway and is required for normal embryonic development. Mutations in the GLI2 gene are associated with type 9 HOLOPROSENCEPHALY and type 2 PALLISTER-HALL SYNDROME. Gli2 Protein
D001003 Anal Canal The terminal segment of the LARGE INTESTINE, beginning from the ampulla of the RECTUM and ending at the anus. Anal Gland, Human,Anal Sphincter,Anus,Anal Gland,Anal Glands, Human,Detrusor External Sphincter,External Anal Sphincter,Internal Anal Sphincter,Anal Sphincter, External,Anal Sphincter, Internal,Anal Sphincters,Detrusor External Sphincters,External Anal Sphincters,Human Anal Gland,Human Anal Glands,Internal Anal Sphincters,Sphincter, Anal,Sphincter, Detrusor External,Sphincter, External Anal,Sphincter, Internal Anal,Sphincters, Anal
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015151 Immunoblotting Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies. Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal

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