ArticleMolecular endocrinology (Baltimore, Md.)2010
A novel isoform of microphthalmia-associated transcription factor inhibits IL-8 gene expression in human cervical stromal cells.
Article in Molecular endocrinology (Baltimore, Md.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- The C-terminal transactivation domain of MITF interacts promiscuously with co-activator CBP/p300.Scientific reports · 2023Article
- The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis.Cell & bioscience · 2021Review
- Microphthalmia transcription factor expression contributes to bone marrow failure in Fanconi anemia.The Journal of clinical investigation · 2020Article
- Myometrial Transcriptional Signatures of Human Parturition.Frontiers in genetics · 2019Article
- Prostaglandin dehydrogenase is a target for successful induction of cervical ripening.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Sohlh2 suppresses epithelial to mesenchymal transition in breast cancer via downregulation of IL-8.Oncotarget · 2016Article
- Agonist-Dependent Downregulation of Progesterone Receptors in Human Cervical Stromal Fibroblasts.Reproductive sciences (Thousand Oaks, Calif.) · 2016Article
- Microphthalmia-associated transcription factor in melanoma development and MAP-kinase pathway targeted therapy.Pigment cell & melanoma research · 2015Review
- Prostaglandin E2 regulates its own inactivating enzyme, 15-PGDH, by EP2 receptor-mediated cervical cell-specific mechanisms.The Journal of clinical endocrinology and metabolism · 2014Article
- PAX6 regulates melanogenesis in the retinal pigmented epithelium through feed-forward regulatory interactions with MITF.PLoS genetics · 2014Article
- The impact of reference gene selection in quantification of gene expression levels in guinea pig cervical tissues and cells.BMC research notes · 2013Article
- Hypoxia and PGE(2) regulate MiTF-CX during cervical ripening.Molecular endocrinology (Baltimore, Md.) · 2012Article
- MITF-M, a 'melanocyte-specific' isoform, is expressed in the adult retinal pigment epithelium.Pigment cell & melanoma research · 2012Article
- Transforming growth factor β1 (TGFβ1) and progesterone regulate matrix metalloproteinases (MMP) in human endometrial stromal cells.The Journal of clinical endocrinology and metabolism · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cervical ripening during pregnancy is a profound change in cervix structure and function characterized by increases in the proinflammatory cytokine IL-8 and dissolution of the cervical extracellular matrix. Relatively little is known about the molecular mechanisms that underlie these events. Here, we report identification of a novel isoform of micropthalmia-associated transcription factor in human cervical stromal cells (MiTF-CX) that is down-regulated 12-fold during cervical ripening and that represses expression of IL-8. Ectopic expression of MiTF-CX in human cervical stromal cells resulted in substantial suppression of endogenous IL-8 mRNA and protein expression, whereas expression of dominant negative MiTF-CX mutants with impaired DNA binding resulted in dramatic increases in IL-8 production. Gel shift, reporter gene, and chromatin immunoprecipitation assays revealed one strong binding site (E-box (-397) CACATG(-391)) in the human IL-8 promoter that was crucial for mediating transcriptional repression by MiTF-CX. Moreover, we show that MiTF-CX expression in the cervix was itself positively autoregulated via two E-box motifs within a 2.1-kb promoter fragment. We therefore propose that maintenance of cervical competency during pregnancy is an active process maintained through suppression of IL-8 by the transcription factor MiTF-CX. During cervical ripening, loss of MiTF-CX would result in significant up-regulation of IL-8 mRNA and protein synthesis, thereby leading to recruitment and activation of leukocytes within the cervix and dissolution of the extracellular matrix.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.