| First Author | Lin L | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 10 | Pages | 2786-2794 |
| PubMed ID | 32998984 | Mgi Jnum | J:304056 |
| Mgi Id | MGI:6502495 | Doi | 10.4049/jimmunol.2000784 |
| Citation | Lin L, et al. (2020) Non-Cell-Autonomous Activity of the Hemidesmosomal Protein BP180/Collagen XVII in Granulopoiesis in Humanized NC16A Mice. J Immunol 205(10):2786-2794 |
| abstractText | 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 DeltaNC16A 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 DeltaNC16A 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 DeltaNC16A mice as compared with wild-type mice. The increased G-CSF was accompanied by an increased activation of the NF-kappaB signaling pathway in bone marrow and BM-MSC of DeltaNC16A mice. Blockade of G-CSF restored normal granulopoiesis in DeltaNC16A mice. Inhibition of NF-kappaB signaling pathway significantly reduces the release of G-CSF from DeltaNC16A BM-MSC in vitro and the level of serum G-CSF in DeltaNC16A mice. To our knowledge, these findings provide the first direct evidence that BP180 plays an important role in granulopoiesis through regulating NF-kappaB signaling pathway in BM-MSC. |
