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. Author manuscript; available in PMC: 2021 Oct 1.
Published in final edited form as: J Thromb Haemost. 2020 Aug 19;18(10):2468–2481. doi: 10.1111/jth.15014

Figure 8. Working model for regulation of lactogenesis by Plg-RKT.

Figure 8.

Plg-RKT regulates key steps essential for nomal lactogenesis. By promoting plasminogen activation, Plg-RKT can exert anti-fibrotic effects by regulating remodeling of the stromal fibrin scaffold, activation of MMP’s for collagen remodeling, and proteolysis of the ECM component, entactin/nidogen-1. Plg-RKT may also exert plasminogen-independent anti-fibrotic effects as mammary gland fibrosis is observed at much earlier time points in lactational development of Plg-RKT−/− glands compared with Plg−/− glands. Plg-RKT may also regulate plasminogen-independent ECM remodeling for lobuloalveolar development as lobuloalveolar development proceeds normally in Plg−/− glands. In addition, Plg-RKT promotes EGF biosynthesis, in a plasminogen-independent fashion, to allow proliferation of epithelial cells to promote lobuloalveolar development. Furthermore, via promoting EGF biosynthesis, Plg-RKT promotes Mcl-1 translation to inhibit apoptosis and maintain alveolar and ductal structure. [Epithelial proliferation and apoptosis are markedly affected by Plg-RKT deletion but are not affected in Plg−/− glands at day 2 of lactation ]. Finally, Plg-RKT can promote plasminogen activation on the surfaces of luminal epithelial cells for fibrin surveillance within the alveoli and ducts to maintain alveolar patency. This diagram has not been published previously.