Mutations in the TRPS1 gene lead to the tricho-rhino-phalangeal syndrome, which is characterized by skeletal defects and abnormal hair development. The TRPS1 gene encodes an atypical member of the GATA-type family of transcription factors. Here we show that mice with a disrupted Trps1 gene develop a chondrodysplasia characterized by diminished chondrocyte proliferation and decreased apoptosis in growth plates. Our analyses revealed that Trps1 is a repressor of Stat3 expression, which in turn controls chondrocyte proliferation and survival by regulating the expression of cyclin D1 and Bcl2. Our conclusion is supported (i) by siRNA-mediated depletion of Stat3 in Trps1-deficient chondrocytes, which normalized the expression of cyclin D1 and Bcl2, (ii) by overexpression of Trps1 in ATDC5 chondrocytes, which diminished Stat3 levels and increased proliferation and apoptosis, and (iii) by mutational analysis of the GATA-binding sites in the Stat3 gene, which revealed that their integrity is critical for the direct association with Trps1 and for Trps1-mediated repression of Stat3. Altogether our findings identify Trps1 as a novel regulator of chondrocytes proliferation and survival through the control of Stat3 expression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ydbio.2007.10.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes.
J Cutan Pathol
January 2025
Department of Pathology and Dermatology, NYU Langone Medical Center, New York, New York, USA.
Background: Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.
Methods: We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel.
Spatial transcriptomics reveals unique metabolic profile and key oncogenic regulators of cervical squamous cell carcinoma.
J Transl Med
December 2024
Tongji Medical College, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430070, China.
Background: As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue.
View Article and Find Full Text PDFSerous-like breast carcinomas: immunophenotypic, genetic, and clinicopathologic characterization of a morphologically distinct group of tumours.
Histopathology
December 2024
Department of Pathology, University of California San Francisco, San Francisco, California, USA.
Aims: Unusual morphologic patterns of breast carcinomas can raise diagnostic consideration for metastasis or special breast cancer subtypes with management implications. We describe rare invasive breast cancers that mimic serous carcinoma of the gynaecologic tract (serous-like breast carcinomas, SLBC) and characterize their clinicopathologic, immunophenotypic, and genetic features.
Methods And Results: All patients were female (n = 15, median age 49 years) without a history of gynaecologic malignancy.
Despite the identification of several dozen genetic loci associated with ischemic stroke (IS), the genetic bases of this disease remain largely unexplored. In this research we present the results of genome-wide association studies (GWAS) based on classical statistical testing and machine learning algorithms (logistic regression, gradient boosting on decision trees, and tabular deep learning model TabNet). To build a consensus on the results obtained by different techniques, the Pareto-Optimal solution was proposed and applied.
View Article and Find Full Text PDFGenomic prediction and genome-wide association studies of morphological traits and distraction index in Korean Sapsaree dogs.
PLoS One
November 2024
Department of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.
Article Synopsis
- The Korean Sapsaree dog is a culturally significant native breed, and this study aimed to enhance genetic improvement and conservation by evaluating breeding values for various traits.
- Researchers analyzed phenotypic data from 378 dogs and performed a genome-wide association study (GWAS) to determine genomic regions affecting traits like body height and hair length.
- Results identified several significant SNPs and candidate genes linked to these traits, suggesting that targeted genomic insights can help improve the breeding quality of the Sapsaree dog.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!