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Diverse Functions of a Disintegrin and Metalloproteinase with Thrombospondin Motif-1

Satoshi Hirohata1, Junko Inagaki2, Takashi Ohtsuki1

  • 1Department of Medical Technology, Graduate School of Health Sciences, Okayama University.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan
|July 5, 2017
PubMed

Insights

A disintegrin and metalloproteinase with thrombospondin motif-1 (ADAMTS1) is induced by stimuli like hypoxia and inflammation. ADAMTS1 plays key roles in angiogenesis and lymphangiogenesis, independent of its protease activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, including ADAMTS1, is crucial for organogenesis and diseases like osteoarthritis.
  • ADAMTS1, the first identified member, is located on chromosome 21 and its expression is rapidly induced by stimuli such as inflammation.

Purpose of the Study:

  • To investigate the expression patterns and functional roles of ADAMTS1.
  • To explore ADAMTS1's involvement in angiogenesis, lymphangiogenesis, and the tumor microenvironment.

Main Methods:

  • Analysis of ADAMTS1 expression in endothelial cells under hypoxic conditions.
  • Measurement of serum ADAMTS1 levels in patients with acute myocardial infarction.
  • Investigation of ADAMTS1 function in ADAMTS1-deficient mice.

Main Results:

  • Hypoxia induces ADAMTS1 expression in endothelial cells.
  • Serum ADAMTS1 levels are elevated in acute myocardial infarction patients and return to normal post-reperfusion.
  • ADAMTS1 exhibits specific roles in angiogenesis and lymphangiogenesis, unrelated to its protease activity.
  • ADAMTS1 appears to have a unique function within the tumor microenvironment.

Conclusions:

  • ADAMTS1 is a rapidly inducible protein with significant roles in vascular and lymphatic development.
  • ADAMTS1's functions in angiogenesis and lymphangiogenesis are independent of its enzymatic activity.
  • ADAMTS1 is implicated in the tumor microenvironment, suggesting diverse biological functions.
Keywords:
angiogenesisextracellular matrixhypoxiamatrix metalloproteinase

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