Upregulation of PPPDE1 contributes to anorectal malformations via the mitochondrial apoptosis pathway during hindgut development in rats
| Autor: | Zheng Wei Yuan, Jing Jing Zhao, Xiao Bing Tang, Yu Zuo Bai, Si Ying Li, Yun Xia Xiao, Cai Yun Long, Chen Yi Wang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Transcriptional Activation Pathology medicine.medical_specialty Apoptosis Biology Immunofluorescence Fetal Development 03 medical and health sciences Urorectal septum 0302 clinical medicine Downregulation and upregulation Carbon-Nitrogen Lyases medicine Animals Humans Cell Proliferation bcl-2-Associated X Protein Gastrointestinal tract medicine.diagnostic_test Cytochromes c Hindgut Cell Biology Embryo Mammalian Anorectal Malformations Mitochondria Rats Blot Gastrointestinal Tract 030104 developmental biology 030220 oncology & carcinogenesis Immunohistochemistry Signal Transduction |
| Zdroj: | Experimental cell research. 402(2) |
| ISSN: | 1090-2422 |
| Popis: | Congenital anorectal malformations (ARMs) are among the most prominent deformities of the gastrointestinal tract; however, their precise aetiology remains obscure. Immunohistochemistry demonstrated that, in the ARM group, the PPPDE1-positive cells were widely distributed in the hindgut epithelial tissue from GD13 to GD16. Immunofluorescence revealed that most TUNEL-, Bax-, and Cytochrome C (Cyt C)-positive cells overlapped with PPPDE1-positive cells in the urorectal septum (URS). Western blotting and quantitative real-time RT-PCR revealed that PPPDE1 levels were significantly higher in the ARM group from GD13 to GD14 (p 0.05). IEC-6 cells were transfected with PPPDE1 overexpression plasmid/NC (negative control) or si-PPPDE1/si-NC. Flow cytometry analysis and CCK-8 assay (used to detect apoptosis and proliferation, respectively), as well as western blotting, showed that the levels of PPPDE1 were positively correlated with the pro-apoptotic molecules Bax and Cyt C. Accordingly, aberrantly high expression of PPPDE1 caused a spatiotemporal imbalance in foetal rats with ARMs during hindgut development. Therefore, the upregulation of PPPDE1 may promote epithelial apoptosis and reduce proliferation in the hindgut via the mitochondrial apoptotic pathway. This could affect the fusion of the URS and cloacal membrane, ultimately inhibiting the hindgut development and resulting in ARMs. |
| Databáze: | OpenAIRE |
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