ADAMTS2, a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) superfamily, is a zinc metalloendopeptidase. It has key functions in extracellular matrix (ECM) remodeling, and is involved in multiple biological pathways such as TGF-β signaling. It is of great biological importance as it contributes to processes like neuronal migration, lymphatic homeostasis, and myofibroblast differentiation [1,2,3]. Genetic models, especially KO mouse models, are valuable in studying its functions.

In the developing neocortex, Adamts2 knockout suppresses the multipolar-to-bipolar transition of migrating neurons and disturbs radial migration, suggesting it promotes radial migration by activating TGF-β signaling [1]. In adult mice, Adamts2 knockout leads to skin lymphedema due to reduced lymphatic vessel density and diameter, indicating its role in pro-VEGFC activation and lymphatic homeostasis [2]. In pancreatic cancer-related studies, loss of Adamts2 reduces myofibroblast differentiation and invasion, with ADAMTS2 regulating myofibroblast differentiation through its role in the regulation of transforming growth factor β availability [3].

In summary, ADAMTS2 is crucial for ECM-related biological processes. KO mouse models have revealed its significance in neocortex development, lymphatic vasculature homeostasis, and pancreatic cancer-associated stromal behavior. Understanding ADAMTS2's functions provides insights into these biological processes and related disease mechanisms.

References:

1. Kaneko, Noe, Hirai, Kumiko, Oshima, Minori, Maeda, Nobuaki, Ohtaka-Maruyama, Chiaki. 2024. ADAMTS2 promotes radial migration by activating TGF-β signaling in the developing neocortex. In EMBO reports, 25, 3090-3115. doi:10.1038/s44319-024-00174-x. https://pubmed.ncbi.nlm.nih.gov/38871984/

2. Dupont, Laura, Joannes, Loïc, Morfoisse, Florent, Noël, Agnès, Colige, Alain Cma. 2022. ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis. In JCI insight, 7, . doi:10.1172/jci.insight.151509. https://pubmed.ncbi.nlm.nih.gov/35316211/

3. Carter, Edward P, Yoneten, Kubra K, Gavara, Nuria, Pearce, Oliver, Grose, Richard P. 2023. Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function. In The Journal of pathology, 262, 90-104. doi:10.1002/path.6214. https://pubmed.ncbi.nlm.nih.gov/37929635/