# 20-hydroxyecdysone promotes brain development via upregulating MMP2 expression during metamorphosis in Helicoverpa armigera

## TL;DR

This study shows that the protein MMP2 helps brain development in a type of insect pest during metamorphosis, and its activity is controlled by a hormone called 20-hydroxyecdysone.

## Contribution

The novel finding is that MMP2 is regulated by 20-hydroxyecdysone via FOXO and is essential for brain development and nutrient supply during insect metamorphosis.

## Key findings

- MMP2 is highly expressed in the brain during metamorphosis and facilitates neural cell proliferation.
- Knockdown of Mmp2 reduces brain development and nutrient levels, and increases autophagy.
- 20-hydroxyecdysone upregulates Mmp2 transcription through the FOXO transcription factor.

## Abstract

Matrix metalloproteinases (MMPs) play crucial roles in both physiological and pathological conditions by degrading the extracellular matrix; however, the roles and regulatory mechanisms of MMPs in brain development remain insufficiently understood. In this study, using the lepidopteran insect Helicoverpa armigera, the cotton bollworm, a serious agricultural pest, as an experimental model, we revealed that MMP2 is an important factor in insect brain development during metamorphosis under steroid hormone 20-hydroxyecdysone (20E) regulation. MMP2 is highly expressed in the brain during metamorphosis. MMP2 is localized in some surface and internal cells in the brain during metamorphosis. The knockdown of Mmp2 by RNA interference in larvae repressed brain development, accompanied by an increase in autophagy and a decrease in cell proliferation. In addition, the nutrient levels of glucose and glutamate decreased in the brain, and the expression of glucose transporters and glutamate transporters decreased after Mmp2 was knocked down. The transcription of Mmp2 was upregulated by 20E via the transcription factor forkhead box O (FOXO) in a time- and concentration-dependent manner. These data suggest that MMP2 facilitates neural cell proliferation and nutrient supply, and ultimately regulates brain development during insect metamorphosis.

This study explores the role of matrix metalloproteinase 2 (MMP2) in brain postembryonic development during metamorphosis in the cotton bollworm, Helicoverpa armigera. Researchers found that MMP2, highly expressed in the brain during metamorphosis under the regulation of the steroid hormone 20-hydroxyecdysone (20E), is crucial for brain development. MMP2 facilitates neural cell proliferation and the accompanying expression of nutrient transporters, thereby ensuring a stable nutrient supply. Knockdown of Mmp2 repressed brain development, reduced nutrient levels (glucose and glutamate), and increased neural cell autophagy, highlighting its roles in regulating neural cell proliferation and maintaining nutrient supply. The study also revealed that 20E upregulates MMP2 expression through the transcription factor FOXO, linking steroid hormonal signaling to brain development. These findings provide insights into postembryonic brain development and may offer new targets for pest control by disrupting metamorphosis. The research underscores the importance of MMP2 in coordinating brain postembryonic development and nutrient dynamics during insect metamorphosis under 20E regulation.