Insulin-like Growth Factor 2 Promotes Tissue-Specific Cell Growth, Proliferation and Survival during Development of Helicoverpa armigera

During development, cells constantly undergo fate choices by differentiating, proliferating, and dying as part of tissue remodeling. However, we only begin to understand the mechanisms of these different fate choices. Here, we took the lepidopteran insect Helicoverpa armigera, the cotton bollworm, as a model to reveal that insulin-like growth factor 2 (IGF-2-like) prevented cell death by promoting cell growth and proliferation. Tissue remodeling occurs during insect metamorphosis from larva to adult under regulation by 20-hydroxyecdysone (20E), a steroid hormone. An unknown insulin-like peptide in the genome of H. armigera was identified as IGF-2-like by sequence analysis using human IGFs. The expression of Igf-2-like was upregulated by 20E. IGF-2-like was localized in the imaginal midgut during tissue remodeling, but not in larval midgut that located nearby. IGF-2-like spread through the fat body during fat body remodeling. Cell proliferation was detected in the imaginal midgut and some fat body cells expressing IGF-2-like. Apoptosis was detected in the larval midgut and some fat body cells that did not express IGF-2-like, suggesting the IGF-2-like was required for cell survival, and IGF-2-like and apoptosis were exclusive, pointing to a survival requirement. Knockdown of Igf-2-like resulted in repression of growth and proliferation of the imaginal midgut and fat body. Our results suggested that IGF-2-like promotes cell growth and proliferation in imaginal tissues, promoting cell death avoidance and survival of imaginal cells during tissue remodeling. It will be interesting to determine whether the mechanism of action of steroid hormones on insulin growth factors is conserved in other species.