Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury.

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Citation

Nanney LB, Skeel A, Luan J, Polis S, Richmond A, Wang MH, Leonard EJ

Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury.

J Invest Dermatol. 1998 Oct;111(4):573-81. doi: 10.1046/j.1523-1747.1998.00332.x.

PubMed ID
9764835 [ View in PubMed
]
Abstract

Macrophage stimulating protein (MSP) exists in blood as inactive pro-MSP. Cleavage yields active MSP, the ligand for a membrane receptor (RON) that is expressed on keratinocytes as well as macrophages. Because both cells have roles in tissue injury, we looked for active MSP and expressed RON in wounds. Concentration of pro-MSP + MSP in wound exudates was in the range for optimal activity. Western blot showed that MSP comprised about half the total, in contrast to less than 10% of the total in blood plasma. The presence of MSP was attributed to an exudate pro-MSP convertase that had an inhibitor profile consistent with a trypsin-like serine protease. Exudate evoked morphologic changes in macrophages in vitro like that of MSP. Removal of this activity by an anti-MSP column shows that exudate stimulation of macrophages is due to MSP. RON was infrequently detected in normal skin. RON protein was markedly upregulated in burn wound epidermis and accessory structures, in proliferating cells or differentiated cells, or both. RON was also detected on macrophages and capillaries. Tissue injury leads to cleavage of pro-MSP to MSP, which has potential to act on keratinocytes, macrophages, and capillaries, all components of the wound healing response.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Macrophage-stimulating protein receptorQ04912Details