scholarly journals Hormonal control of plasmin and tissue-type plasminogen activator activity in rat milk during involution of the mammary gland

2000 ◽  
Vol 167 (2) ◽  
pp. 265-273 ◽  
Author(s):  
E Tonner ◽  
GJ Allan ◽  
DJ Flint
Keyword(s):  
Mammary Gland ◽  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Plasminogen Activation ◽  
Insulin Like Growth Factor ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Igf I ◽  
Pai 1

We have proposed that growth hormone (GH) and prolactin (PRL) interact to suppress apoptosis in the mammary gland. GH increases insulin-like growth factor-I (IGF-I) synthesis whereas PRL suppresses the production of insulin-like growth factor-binding protein-5 (IGFBP-5) in the epithelial cells, which would otherwise inhibit IGF-mediated cell survival. IGFBP-5 was present in milk from involuting glands at high concentrations (approximately 60 microg/ml) and had a high affinity (8.03 x 10(-10) M) for IGF-I, suggesting an inhibitory effect of IGFBP-5 in the mammary gland. IGFBP-5 was present in the micellar fraction of milk and binds specifically to alpha(s2)-casein. Since alpha(s2)-casein also binds plasminogen and tissue-type plasminogen activator (t-PA), resulting in the conversion of plasminogen to plasmin, and since IGFBP-5 binds to plasminogen activator inhibitor-1 (PAI-1), we investigated whether apoptosis and extracellular matrix (ECM) degradation might be coordinately controlled by GH and PRL possibly acting through IGFBP-5. Litters were removed from lactating rats to initiate involution. Plasminogen activation and t-PA activity were both increased dramatically after 48 h and GH and PRL suppressed this response. By contrast, 17beta-oestradiol, progesterone or corticosterone did not influence either process. An antiserum to IGF-I, which blocked systemic IGF-I effects, failed to inhibit the activation of plasminogen or the increase in t-PA, suggesting that paracrine effects of IGF-I may be more important. Teat-sealing, which led to the accumulation of milk without hormonal changes, also led to increases in plasminogen activation and t-PA activity, suggesting that locally produced factors (of which IGFBP-5 is one) are important in controlling ECM remodelling. We propose that GH and PRL inhibit apoptosis and ECM remodelling by a process that involves the control of IGF-I and PAI-1 availability by IGFBP-5, thus allowing these processes to be tightly coordinated.

Inhibition of PAI-1 induces neutrophil-driven neoangiogenesis and promotes tissue regeneration via production of angiocrine factors in mice

Blood ◽  
2012 ◽  
Vol 119 (26) ◽  
pp. 6382-6393 ◽  
Author(s):  
Yoshihiko Tashiro ◽  
Chiemi Nishida ◽  
Kaori Sato-Kusubata ◽  
Makiko Ohki-Koizumi ◽  
Makoto Ishihara ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Regeneration ◽  
Immunohistochemical Analysis ◽  
Angiogenic Factor ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Pai 1

Abstract Plasminogen activator inhibitor-1 (PAI-1), an endogenous inhibitor of a major fibrinolytic factor, tissue-type plasminogen activator, can both promote and inhibit angiogenesis. However, the physiologic role and the precise mechanisms underlying the angiogenic effects of PAI-1 remain unclear. In the present study, we report that pharmacologic inhibition of PAI-1 promoted angiogenesis and prevented tissue necrosis in a mouse model of hind-limb ischemia. Improved tissue regeneration was due to an expansion of circulating and tissue-resident granulocyte-1 marker (Gr-1+) neutrophils and to increased release of the angiogenic factor VEGF-A, the hematopoietic growth factor kit ligand, and G-CSF. Immunohistochemical analysis indicated increased amounts of fibroblast growth factor-2 (FGF-2) in ischemic gastrocnemius muscle tissues of PAI-1 inhibitor-treated animals. Ab neutralization and genetic knockout studies indicated that both the improved tissue regeneration and the increase in circulating and ischemic tissue-resident Gr-1+ neutrophils depended on the activation of tissue-type plasminogen activator and matrix metalloproteinase-9 and on VEGF-A and FGF-2. These results suggest that pharmacologic PAI-1 inhibition activates the proangiogenic FGF-2 and VEGF-A pathways, which orchestrates neutrophil-driven angiogenesis and induces cell-driven revascularization and is therefore a potential therapy for ischemic diseases.

scholarly journals Cell-Free mRNA Concentrations of Plasminogen Activator Inhibitor-1 and Tissue-Type Plasminogen Activator Are Increased in the Plasma of Pregnant Women with Preeclampsia

2007 ◽  
Vol 53 (3) ◽  
pp. 399-404 ◽  
Author(s):  
Yuditiya Purwosunu ◽  
Akihiko Sekizawa ◽  
Keiko Koide ◽  
Antonio Farina ◽  
Noroyono Wibowo ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Plasminogen Activator ◽  
Plasminogen Activator Inhibitor ◽  
Maternal Plasma ◽  
Tissue Type ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background: Detection of placental mRNA in maternal plasma has been reported in high-risk pregnancies. We attempted to investigate the concentrations of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (tPA) mRNA in maternal plasma in preeclampsia. Methods: Peripheral blood samples were obtained from healthy pregnant women before and after delivery and also from women with or without preeclampsia. Plasma was isolated from these samples, and RNA was extracted. Plasma PAI-1 and tPA mRNA concentrations were then measured by use of reverse transcription PCR assays. The concentrations were converted into multiples of the median (MoM) of the controls adjusted for gestational age. Data were stratified and analyzed according to the clinical severity of preeclampsia and quantitative distribution of blood pressure and proteinuria. Results: The median (minimum–maximum) PAI-1 mRNA MoM values for women with preeclampsia and controls were 2.48 (0.82–8.53) and 1.00 (0.41–2.33), respectively, whereas the median (minimum–maximum) tPA mRNA MoM values were 3.33 (1.01–10.58) and 1.00 (0.95–1.20), respectively. The concentrations of both PAI-1 and tPA mRNA were significantly increased in cases of preeclampsia, compared with controls (P <0.0001). The MoM values of both mRNA species were directly correlated with the severity of preeclampsia and were greatest among a subgroup of hemolysis, increased liver enzymes, and low platelets pregnancies. Conclusion: Maternal plasma PAI-1 and tPA mRNAs are significantly increased in patients with preeclampsia and are positively correlated with the severity of preeclampsia.

scholarly journals Tissue-type plasminogen activator is not necessary for platelet-derived growth factor-c activation

2014 ◽  
Vol 1842 (2) ◽  
pp. 318-325 ◽  
Author(s):  
Kimberly J. Riehle ◽  
Melissa M. Johnson ◽  
Fredrik Johansson ◽  
Renay L. Bauer ◽  
Brian J. Hayes ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Platelet Derived Growth Factor ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Factor C

scholarly journals Localization in the fibrinogen γ-chain of a new site that is involved in the acceleration of the tissue-type plasminogen activator-catalysed activation of plasminogen

1992 ◽  
Vol 283 (1) ◽  
pp. 187-191 ◽  
Author(s):  
O Yonekawa ◽  
M Voskuilen ◽  
W Nieuwenhuizen
Keyword(s):  
Plasminogen Activator ◽  
Sequence Data ◽  
Disulphide Bond ◽  
Void Volume ◽  
Tissue Type ◽  
Plasminogen Activation ◽  
Main Band ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Water Ph

In previous publications [e.g. Voskuilen, Vermond, Veeneman, Van Boom, Klasen, Zegers & Nieuwenhuizen (1987) J. Biol. Chem. 262, 5944-5946] we have shown that fibrin(ogen) chain fragment A alpha-(148-160) contains a site that contributes to the acceleration of Glu-plasminogen activation by tissue-type plasminogen activator (t-PA). In contrast with fibrin, this peptide, however, does not enhance the rate of mini-plasminogen activation. Therefore, possibly more stimulatory sites than A alpha-(148-160) are present in fibrin. In the present investigation we have localized a possible second type of stimulatory site in the fibrin(ogen) molecule. A whole CNBr digest of fibrinogen was applied to a Bio-Gel P-2 column run in water, pH 4. Two peaks with stimulatory activity were observed, one at the void volume and one between the void volume and the total volume. The former contained the previously described stimulating fragment FCB-2 [which comprises A alpha-(148-160)]; the latter had not been observed before and was characterized further. The stimulating material in the low-M(r) fraction of the Bio-Gel P-2 column was precipitated at pH 8.3 in a virtually pure form. It has a high tryptophan content, and an M(r) of 6500 as assessed by SDS/PAGE. On reduction, a main band of M(r) 2500 is seen, plus a weakly staining band of M(r) 4000. These properties plus the amino acid sequence data identify the fragment as FCB-5. FCB-5 consists of two chains, i.e. gamma-(311-336) and gamma-(337-379), linked by a single disulphide bond between Cys-gamma-326 and Cys-gamma-339. Both these chains and the disulphide bond appear to be essential for rate enhancement. FCB-5 enhances the activation rates of Glu-, mini- and micro-plasminogen, with all five kringles, only kringle V and without kringles respectively. FCB-5 binds t-PA, but none of the plasminogen forms binds to FCB-5. This indicates that the rate enhancements induced by FCB-5 are due to an effect on t-PA.

scholarly journals Tetranectin binds hepatocyte growth factor and tissue-type plasminogen activator

2003 ◽  
Vol 270 (8) ◽  
pp. 1850-1854 ◽  
Author(s):  
Uffe B. Westergaard ◽  
Mikkel H. Andersen ◽  
Christian W. Heegaard ◽  
Sergey N. Fedosov ◽  
Torben E. Petersen
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Plasminogen Activator ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Hepatocyte Growth
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