Abstract
Objective: To determine if A-kinase anchoring protein 13 (AKAP13) interacts with the vitamin D receptor (VDR) to alter vitamin D-dependent signaling in fibroid cells. Uterine leiomyomas (fibroids) are characterized by a fibrotic extracellular matrix and are associated with vitamin D deficiency. Treatment with vitamin D (1,25-dihydroxyvitamin D3) reduces fibroid growth and extracellular matrix gene expression. A-kinase anchoring protein 13 is overexpressed in fibroids and interacts with nuclear hormone receptors, but it is not known whether AKAP13 may interact with the VDR to affect vitamin D signaling in fibroids. Design: Laboratory studies. Setting: Translational science laboratory. Intervention(s): Human immortalized fibroid or myometrial cells were treated with 1,25-hydroxyvitamin D3 (1,25(OH)2D3) and transfected using expression constructs for AKAP13 or AKAP13 mutants, RhoQL, C3 transferase, or small interfering ribonucleic acids (RNAs). Main Outcome Measure(s): Messenger ribonucleic acid (mRNA) levels of AKAP13, fibromodulin, and versican as measured by quantitative real-time polymerase chain reaction. Glutathione S-transferase-binding assays. Vitamin D-dependent gene activation as measured by luciferase assays. Result(s): 1,25(OH)2D3 resulted in a significant reduction in mRNA levels encoding AKAP13, versican, and fibromodulin. Small interfering RNA silencing of AKAP13 decreased both fibromodulin and versican mRNA levels. Glutathione S-transferase-binding assays revealed that AKAP13 bound to the VDR through its nuclear receptor interacting region. Cotransfection of AKAP13 and VDR significantly reduced vitamin D-dependent gene activation. RhoA pathway inhibition partially relieved repression of vitamin D-dependent gene activation by AKAP13. Conclusion(s): These data suggest that AKAP13 inhibited the vitamin D receptor activation by a mechanism that required, at least in part, RhoA activation.
Original language | English (US) |
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Pages (from-to) | 303-314 |
Number of pages | 12 |
Journal | F and S Science |
Volume | 2 |
Issue number | 3 |
DOIs | |
State | Published - Aug 2021 |
Keywords
- AKAP13
- BRX
- Vitamin D
- extracellular matrix
- uterine leiomyoma
- vitamin D deficiency
ASJC Scopus subject areas
- Reproductive Medicine
- Embryology