Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution

Jennifer N. Lilla, Ravi V. Joshi, Charles S. Craik, Zena Werb

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The plasminogen cascade of serine proteases directs both development and tumorigenesis in the mammary gland. Plasminogen can be activated to plasmin by urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasma kallikrein (PKal). The dominant plasminogen activator for mammary involution is PKal, a serine protease that participates in the contact activation system of blood coagulation. We observed that the prekallikrein gene (Klkb1) is expressed highly in the mammary gland during stromal remodeling periods including puberty and postlactational involution. We used a variant of ecotin (ecotin-PKal), a macromolecular inhibitor of serine proteases engineered to be highly specific for active PKal, to demonstrate that inhibition of PKal with ecotin-PKal delays alveolar apoptosis, adipocyte replenishment, and stromal remodeling in the involuting mammary gland, producing a phenotype resembling that resulting from plasminogen deficiency. Using biotinylated ecotin-PKal, we localized active PKal to connective tissue-type mast cells in the mammary gland. Taken together, these results implicate PKal as an effector of the plasminogen cascade during mammary development.

Original languageEnglish (US)
Pages (from-to)13792-13803
Number of pages12
JournalJournal of Biological Chemistry
Volume284
Issue number20
DOIs
StatePublished - May 15 2009

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Plasma Kallikrein
Human Mammary Glands
Adipocytes
Mast Cells
Epithelial Cells
Apoptosis
Plasminogen
Serine Proteases
Breast
Prekallikrein
Connective Tissue Cells
Serine Proteinase Inhibitors
Plasminogen Activators
Fibrinolysin
Urokinase-Type Plasminogen Activator
Blood Coagulation
Tissue Plasminogen Activator
Puberty
Coagulation
Carcinogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. / Lilla, Jennifer N.; Joshi, Ravi V.; Craik, Charles S.; Werb, Zena.

In: Journal of Biological Chemistry, Vol. 284, No. 20, 15.05.2009, p. 13792-13803.

Research output: Contribution to journalArticle

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