Secreted protease ADAMTS18 in development and disease

Area of Science:

• Biochemistry
• Developmental Biology
• Genetics

Background:

• ADAMTS18 (A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18) is a secreted metalloproteinase identified in 2002.
• Previously, ADAMTS18 was primarily recognized as a candidate gene linked to pathologies like malignancies and eye disorders.
• Its functions and substrates under normal physiological conditions remained largely unknown before 2016.

Purpose of the Study:

• To review the current understanding of ADAMTS18's functions, substrates, and regulators.
• To highlight the significance of ADAMTS18 in normal physiological conditions based on recent in vivo studies.
• To discuss the challenges in translating research findings on ADAMTS18 into clinical applications.

Main Methods:

• Review of scientific literature published since 2016, focusing on studies utilizing Adamts18 knockout models.
• Analysis of data from in vivo studies investigating the physiological roles of ADAMTS18.
• Synthesis of information on ADAMTS18 substrates and regulatory mechanisms.

Main Results:

• ADAMTS18 is essential for the proper morphology and organogenesis of multiple epithelial organs, including the lung, kidney, breast, salivary, and lacrimal glands.
• The gene plays a vital role in the development and function of vascular and neuronal systems, adipose tissue, and reproductive tracts.
• Recent studies have elucidated key substrates and regulators of ADAMTS18 activity.

Conclusions:

• ADAMTS18 is a critical regulator of organogenesis and tissue homeostasis in vivo.
• Understanding ADAMTS18's normal functions provides insights into its potential roles in disease.
• Further research is needed to bridge the gap between experimental findings and clinical translation for ADAMTS18.