Lack of plasminogen leads to milk stasis and premature mammary gland involution during lactation |
| |
Authors: | Green Kirsty A Nielsen Boye S Castellino Francis J Rømer John Lund Leif R |
| |
Institution: | Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK-2100, Copenhagen, Denmark. |
| |
Abstract: | The extracellular serine protease, plasmin, is activated from its precursor, plasminogen (Plg), by the urokinase-type and tissue-type Plg activators (uPA and tPA respectively). One of the main plasmin substrates, fibrin, is formed from fibrinogen via thrombin activity. We have previously shown that mice deficient for Plg are strikingly less able to support a litter during lactation compared to wild type mice. Here we suggest a mechanism responsible for this lactation defect. Reduced epithelial content and increased apoptosis are observed in Plg-deficient mammary glands at lactation day 7. Immunofluorescence analysis reveals the presence of fibrin(ogen) in the stroma surrounding mammary alveoli and adipocytes and identifies fibrin(ogen) as a component of breast milk in both wild type and Plg-deficient mice. Furthermore, a large accumulation of fibrin(ogen) together with apoptotic epithelial cells is observed in the lactating mammary alveoli and ducts of some Plg-deficient mice. This suggests that fibrin plays a key role in the malfunction of mammary glands in the absence of Plg, possibly through blockade of mammary ducts inducing milk stasis, inhibiting milk expulsion and thereby inducing premature apoptosis and involution. |
| |
Keywords: | BM basement membrane BrdU 5-bromo-2-deoxy-uridine Fib fibrinogen ECM extracellular matrix MMP matrix metalloprotease PAI-1 plasminogen activator inhibitor-1 Plg plasminogen TEBs terminal end buds tPA tissue plasminogen activator uPA urokinase plasminogen activator |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|