Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice.

Journal Article (Journal Article)

BP180 (also termed type XVII collagen) is a hemidesmosomal protein and plays a critical role in cell-cell matrix adhesion in the skin; however, its other biological functions are largely unclear. In this study, we generated a BP180 functional-deficient mouse strain by deleting its extracellular domain of humanized NC16A (termed ΔNC16A mice). We found that BP180 is expressed by bone marrow mesenchymal stem cells (BM-MSC), and its functional deficiency leads to myeloid hyperplasia. Altered granulopoiesis in ΔNC16A mice is through bone marrow stromal cells evidenced by bone marrow transplantation. Furthermore, the level of G-CSF in bone marrow and circulation were significantly increased in ΔNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-κB signaling pathway in bone marrow and BM-MSC of ΔNC16A mice. Blockade of G-CSF restored normal granulopoiesis in ΔNC16A mice. Inhibition of NF-κB signaling pathway significantly reduces the release of G-CSF from ΔNC16A BM-MSC in vitro and the level of serum G-CSF in ΔNC16A mice. To our knowledge, these findings provide the first direct evidence that BP180 plays an important role in granulopoiesis through regulating NF-κB signaling pathway in BM-MSC.

Full Text

Duke Authors

Cited Authors

  • Lin, L; Hwang, B-J; Li, N; Googe, P; Diaz, LA; Miao, E; Vilen, B; Thomas, NE; Ting, J; Liu, Z

Published Date

  • November 2020

Published In

Volume / Issue

  • 205 / 10

Start / End Page

  • 2786 - 2794

PubMed ID

  • 32998984

Pubmed Central ID

  • PMC7658030

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.2000784

Language

  • eng