| 1. |
- Li, Jinan, et al.
(författare)
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The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis.
- 2005
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Ingår i: American Journal of Pathology. - New York : Elsevier. - 0002-9440 .- 1525-2191. ; 166:3, s. 783-792
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Tidskriftsartikel (refereegranskat)abstract
- The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoimmune collagen type II (CII)-induced arthritis (CIA) model and mice deficient for urokinase-type PA (uPA) or plasminogen to investigate the role of the PA system for development of arthritis. Our data revealed that uPA-deficient mice have a lower severity and incidence of CIA than wild-type mice. Furthermore, although >80% of wild-type control mice developed CIA, we found that none of the 50 plasminogen-deficient littermates that were tested developed CIA within a 40-day period. Antibody generation after CII immunization as well as the binding of labeled anti-CII antibodies to the surface of cartilage were similar in wild-type and plasminogen-deficient mice. No sign of inflammation was seen when plasminogen-deficient mice were injected with a mixture of monoclonal antibodies against CII. However, after daily injections of human plasminogen, these mice developed arthritis within 5 days. Our finding that infiltration of inflammatory cells into the synovial joints was impaired in plasminogen-deficient mice suggests that uPA and plasminogen are important mediators of joint inflammation. Active plasmin is therefore essential for the induction of pathological inflammatory joint destruction in CIA.
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| 2. |
- Liu, Kui, et al.
(författare)
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Successful ovulation in plasminogen-deficient mice treated with the broad-spectrum matrix metalloproteinase inhibitor galardin.
- 2006
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Ingår i: Developmental Biology. - New York : Academic P.. - 0012-1606 .- 1095-564X. ; 295:2, s. 615-622
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Tidskriftsartikel (refereegranskat)abstract
- Many studies have suggested the hypothesis that the plasminogen activator (PA) system and the matrix metalloproteinase (MMP) system, either separately or in combination, may provide the proteolytic activity that is required for rupture of the follicular wall at the time of ovulation. Our recent studies on ovulation in plasminogen (plg)-deficient mice have, however, shown that plasmin is not required for normal ovulation, leading us to the hypothesis that MMPs may be a more important source of proteolysis for this process. To investigate the role of MMPs and also the possibility of a functional overlap or synergy between the MMP and PA systems during ovulation, we have studied ovulation efficiency in wild-type and plg-deficient mice treated with the broad-spectrum MMP inhibitor galardin. We found that in both wild-type mice and heterozygous plg-deficient (plg(+/-)) mice that had been treated with galardin prior to ovulation, there was a mild (18-20%) reduction in ovulation efficiency. Surprisingly, galardin treatment of plg-deficient (plg(-/-)) mice only caused an additional 14% reduction in ovulation efficiency as compared to vehicle-treated plg(-/-) mice. Our data therefore suggest that although MMPs may play a role in degradation of the follicular wall, they may not be obligatory for ovulation. In contrast to previous studies on tissue remodeling during wound heating and placental development, we have demonstrated that there is no obvious functional overlap or synergy between the PA and MMP systems, which has previously been thought to be essential for the ovulatory process.
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| 3. |
- Li, Xuri, et al.
(författare)
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Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors
- 2005
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 115:1, s. 118-127
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Tidskriftsartikel (refereegranskat)abstract
- The angiogenic mechanism and therapeutic potential of PDGF-CC, a recently discovered member of the VEGF/PDGF superfamily, remain incompletely characterized. Here we report that PDGF-CC mobilized endothelial progenitor cells in ischemic conditions; induced differentiation of bone marrow cells into ECs; and stimulated migration of ECs. Furthermore, PDGF-CC induced the differentiation of bone marrow cells into smooth muscle cells and stimulated their growth during vessel sprouting. Moreover, delivery of PDGF-CC enhanced postischemic revascularization of the heart and limb. Modulating the activity of PDGF-CC may provide novel opportunities for treating ischemic diseases.
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