例如:"lncRNA", "apoptosis", "WRKY"

The metalloproteinase Papp-aa controls epithelial cell quiescence-proliferation transition.

Elife. 2020 Apr 16;9
Chengdong Liu 1 , Shuang Li 2 , Pernille Rimmer Noer 3 , Kasper Kjaer-Sorensen 3 , Anna Karina Juhl 3 , Allison Goldstein 1 , Caihuan Ke 2 , Claus Oxvig 3 , Cunming Duan 1
Chengdong Liu 1 , Shuang Li 2 , Pernille Rimmer Noer 3 , Kasper Kjaer-Sorensen 3 , Anna Karina Juhl 3 , Allison Goldstein 1 , Caihuan Ke 2 , Claus Oxvig 3 , Cunming Duan 1
+ et al

[No authors listed]

Author information
  • 1 Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, United States.
  • 2 College of Ocean and Earth Sciences, Xiamen University, Xiamen, China.
  • 3 Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.

摘要


Human patients carrying PAPP-A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

KEYWORDS: Ca2+ deficiency, IGF signaling, IGFBP5, STC, developmental biology, pappalysin, zebrafish