Steroid signaling in mature follicles is important for Drosophila ovulation

Although ecdysteroid signaling regulates multiple steps in oogenesis, it is not known whether it regulates Drosophila ovulation, a process involving a matrix metalloproteinase-dependent follicle rupture. In this study, we demonstrated that ecdysteroid signaling is operating in mature follicle cells to control ovulation. Moreover, knocking down shade (shd), encoding the monooxygenase that converts ecdysone (E) to the more active 20-hydroxyecdysone (20E), specifically in mature follicle cells, blocked follicle rupture, which was rescued by ectopic expression of shd or exogenous 20E. In addition, disruption of the Ecdysone receptor (EcR) in mature follicle cells mimicked shd-knockdown defects, which were reversed by ectopic expression of EcR.B2 but not by EcR.A or EcR.B1 isoforms. Furthermore, we showed that ecdysteroid signaling is essential for the proper activation of matrix metalloproteinase 2 (Mmp2) for follicle rupture. Our data strongly suggest that 20E produced in follicle cells before ovulation activates EcR.B2 to prime mature follicles to be responsive to neuronal ovulatory stimuli, thus providing mechanistic insights into steroid signaling in Drosophila ovulation.

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The miR-29b/Matrix Metalloproteinase 2 Axis Regulates Transdifferentiation and Calcification of Vascular Smooth Muscle Cells in a Calcified Environment

Blood Purification ◽

10.1159/000505571 ◽

2020 ◽

Vol 49 (5) ◽

pp. 524-534 ◽

Cited By ~ 2

Author(s):

Wenhong Jiang ◽

Zhanman Zhang ◽

Han Yang ◽

Qiuning Lin ◽

Xiao Qin

Keyword(s):

Smooth Muscle ◽

Matrix Metalloproteinase ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Ectopic Expression ◽

Muscle Cells ◽

Matrix Metalloproteinase 2 ◽

High Calcium

Background: Vascular calcification (VC) is a common pathological lesion that promotes progress and mortality in cardiovascular disease. Vascular smooth muscle cells (VSMCs) acquiring an osteogenic phenotype facilitate VC occurrence and development. We recently reported that miR-29b-3p directly regulates the expression of matrix metalloproteinase 2 (MMP2). Herein, we test whether miR-29b-3p functions in the phenotypic transition and calcification in a calcified environment. Methods and Results: VSMC calcification in vitro was induced with calcification medium containing β-glycerophosphoric acid or high calcium. MiR-29b-3p expression in VSMCs tended to decrease during culturing in calcification medium. MiR-29b-3p overexpression ameliorated VSMC calcification, whereas miR-29b-3p knockdown exacerbated VSMC calcification. Furthermore, ectopic expression of miR-29b-3p inhibited the expression of osteogenic markers and MMP2 (a known target gene of miR-29b-3p). By contrast, miR-29b-3p deficiency facilitated VSMC osteogenesis differentiation and upregulated MMP2 expression. Conclusion: Our research suggests that miR-29b-3p regulates VSMC calcification and osteogenesis differentiation, at least in part, by targeting MMP2. Regulation of miR-29b-3p expression is therefore a potential therapeutic target for VSMC calcification.

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NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1800115115 ◽

2018 ◽

Vol 115 (30) ◽

pp. 7765-7770 ◽

Cited By ~ 9

Author(s):

Wei Li ◽

Jessica F. Young ◽

Jianjun Sun

Keyword(s):

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Nadph Oxidase ◽

Signaling Pathway ◽

Reactive Oxygen ◽

Follicle Cells ◽

Matrix Metalloproteinase 2 ◽

Oxygen Species ◽

Follicle Rupture

Ovarian reactive oxygen species (ROS) are believed to regulate ovulation in mammals, but the details of ROS production in follicles and the role of ROS in ovulation in other species remain underexplored. In Drosophila ovulation, matrix metalloproteinase 2 (MMP2) is required for follicle rupture by degradation of posterior follicle cells surrounding a mature oocyte. We recently demonstrated that MMP2 activation and follicle rupture are regulated by the neuronal hormone octopamine (OA) and the octopamine receptor in mushroom body (OAMB). In the current study, we investigated the role of the superoxide-generating enzyme NADPH oxidase (NOX) in Drosophila ovulation. We report that Nox is highly enriched in mature follicle cells and that Nox knockdown in these cells leads to a reduction in superoxide and to defective ovulation. Similar to MMP2 activation, NOX enzymatic activity is also controlled by the OA/OAMB-Ca2+ signaling pathway. In addition, we report that extracellular superoxide dismutase 3 (SOD3) is required to convert superoxide to hydrogen peroxide, which acts as the key signaling molecule for follicle rupture, independent of MMP2 activation. Given that Nox homologs are expressed in mammalian follicles, the NOX-dependent hydrogen peroxide signaling pathway that we describe could play a conserved role in regulating ovulation in other species.

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