17 September 2019 : Clinical Research
Retinoic Acid Promotes Retinoic Acid Signaling by Suppression of Pitx1 In Tendon Cells: A Possible Mechanism of a Clubfoot-Like Phenotype Induced by Retinoic AcidXiang Zhao1ABCEF, Xuan Yang1ABCDEFG*
Med Sci Monit 2019; 25:6980-6989
BACKGROUND: The pathogenesis of idiopathic congenital clubfoot (CCF) is unknown. Although some familial patients have Pitx1 mutations, and the Pitx1+/– genotype causes a clubfoot-like phenotype in mice, the mechanism of Pitx1-induced CCF is unknown.
MATERIAL AND METHODS: We used tibialis anterior tendon samples to detect the expression of Pitx1 in idiopathic and neurogenic clubfoot patients. After obtaining Sprague-Dawley (SD) rat Achilles tendon cells, the expression of Pitx1 was knocked down by SiRNA. After 48 h of culture, mass spectrometry was used to quantitatively analyze proteins. Then, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to assess the downstream pathway of PITX1. The relationship between Pitx1 and the promoter region of deacetylase 1 (Sirtuin-1 and Sirt1) was examined by luciferase and ChIP assays.
RESULTS: We found that Pitx1 expression in the tendon samples of idiopathic CCF patients was downregulated. Mass spectrometry analysis revealed that the inhibition of Pitx1 induced the downregulation of Sirt1 expression in tendon cells. Luciferase and ChIP assays confirmed that Pitx1 binds to the promoter region of SIRT1 and promotes Sirt1 gene transcription. Further results showed that, after the inhibition of Pitx1 in tendon cells, CRABP2 acetylation increased, the nuclear import of CRABP2 was enhanced, and the expression of RARβ2 increased. After the inhibition of Pitx1, RARβ2 expression was further increased by RA treatment in tendon cells. In the presence of retinoic acid, the expression of Pitx1 was inhibited in tendon cells.
CONCLUSIONS: Pitx1 binds to the promoter region of SIRT1 and promotes the transcription of SIRT1. Positive feedback occurs between RA signaling and Pitx1.
Keywords: Achilles Tendon, Clubfoot, sirtuin 1
25 October 2021 : EditorialEditorial: The 2021 European Society of Cardiology (ESC) Guidelines on the Real-World Prevention of Atherosclerotic Cardiovascular Disease (ASCVD)
Med Sci Monit 2021; 27:e935172
22 October 2021 : Clinical ResearchA Novel Method for the Production of an Autologous Anti-Inflammatory and Anti-Catabolic Product (Cytorich) ...
Med Sci Monit In Press; DOI: 10.12659/MSM.934365
11 October 2021 : Clinical ResearchClinical Features and Temporal Lung Radiographic Changes in 25 Patients Recovering from COVID-19 Pneumonia:...
Med Sci Monit In Press; DOI: 10.12659/MSM.933381
08 September 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit In Press; DOI: 10.12659/MSM.932788
27 Oct 2021 : Clinical ResearchUse of the Braden Scale to Predict Injury Severity in Mass Burn Casualties
Med Sci Monit In Press; DOI: 10.12659/MSM.934039
27 Oct 2021 : Database AnalysisLow Expression of Long Noncoding RNA SLC26A4 Antisense RNA 1 Is an Independent Prognostic Biomarker and Cor...
Med Sci Monit In Press; DOI: 10.12659/MSM.934522
27 Oct 2021 : Database AnalysisA Novel Predictive Model Incorporating Ferroptosis-Related Gene Signatures for Overall Survival in Patients...
Med Sci Monit In Press; DOI: 10.12659/MSM.934050
Most Viewed Current Articles
20 Mar 2020 : Clinical ResearchSocial Capital and Sleep Quality in Individuals Who Self-Isolated for 14 Days During the Coronavirus Diseas...
Med Sci Monit 2020; 26:e923921
15 Apr 2020 : Clinical ResearchPsychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...
Med Sci Monit 2020; 26:e924171
05 May 2020 : Review articleAn Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development
Med Sci Monit 2020; 26:e924700