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

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.