Serum inter-alpha-trypsin inhibitor and matrix hyaluronan promote angiogenesis in fibrotic lung injury.
ABSTRACT The etiology and pathogenesis of angiogenesis in idiopathic pulmonary fibrosis (IPF) is poorly understood. Inter-alpha-trypsin inhibitor (IaI) is a serum protein that can bind to hyaluronan (HA) and may contribute to the angiogenic response to tissue injury.
To determine whether IaI promotes HA-mediated angiogenesis in tissue injury.
An examination was undertaken of angiogenesis in IaI-sufficient and -deficient mice in the bleomycin model of pulmonary fibrosis and in angiogenesis assays in vivo and in vitro. IaI and HA in patients with IPF were examined.
IaI significantly enhances the angiogenic response to short-fragment HA in vivo and in vitro. lal deficiency Ieads to decreased angiogenesis in the matrigel model, and decreases lung angiogenesis after bleomycin exposure in mice. IaI is found in fibroblastic foci in IPF, where it colocalizes with HA. The colocalization is particularly strong in vascular areas around fibroblastic foci. Serum levels of IaI and HA are significantly elevated in patients with IPF compared with control subjects. High serum IaI and HA levels are associated with decreased lung diffusing capacity, but not FVC.
Our findings indicate that serum IaI interacts with HA, and promotes angiogenesis in lung injury. IaI appears to contribute to the vascular response to lung injury and may lead to aberrant angiogenesis. Clinical trial registered with www.clinicaltrials.gov (NCT00016627).
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ABSTRACT: An understanding of the basic reproductive physiology is essential for achieving increases in collared peccary productivity. We characterized the major proteins of the peccary seminal plasma, based on semen samples collected from nine adult and reproductively sound animals. Our approach included the use of 2-D electrophoresis followed by Coomassie blue staining and analysis of polypeptide maps with PDQuest software (Bio Rad,USA). Proteins were identified by tandem mass spectrometry (LC-MS/MS). We identity 93 spots in the 2-D gels, corresponding to 23 proteins. Such spots represent the major proteins expressed in the peccary seminal plasma given that their intensities are equivalent to 83.6 % of the intensities of all spots of depicted in the master gel and 94.5 % of all spots detected in every protein map. Spermadhesin porcine seminal plasma protein 1, clusterin and bodhesin 2 were the most abundant proteins, equivalent to 20.9%, 19.8% and 10.2%, respectively, of the total intensity of valid spots in the gels. Furthermore, the intensity of a clusterin spot had a negative association (r = -0.87; p < 0.05) with the percentage of sperm with functional membrane. We observed a polymorphic pattern in the seminal plasma map, as several proteins were expressed with isoforms, such as clusterin (27 spots) and glutathione peroxidase (12 spots), among others. In conclusion, the present study is the first to describe the major proteomic map of the seminal plasma of Pecari tajacu.Reproduction 02/2014; DOI:10.1530/REP-13-0220
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ABSTRACT: Hyaluronan (HA), a major component of the extracellular matrix (ECM), plays a key role in regulating inflammation. Inflammation is associated with accumulation and turnover of HA polymers by multiple cell types. Increasingly through the years, HA has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes. HA and its binding proteins regulate the expression of inflammatory genes, the recruitment of inflammatory cells, the release of inflammatory cytokines, and can attenuate the course of inflammation, providing protection against tissue damage. A growing body of evidence suggests the cell responses are HA molecular weight dependent. HA fragments generated by multiple mechanisms throughout the course of inflammatory pathologies, elicit cellular responses distinct from intact HA. This review focuses on the role of HA in the promotion and resolution of inflammation.Frontiers in Immunology 03/2014; 5:101. DOI:10.3389/fimmu.2014.00101
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ABSTRACT: We have previously demonstrated that the Src family kinase Yes, the Yes-associated protein (YAP) and TEA domain TEAD2 transcription factor pathway are activated by leukemia inhibitory factor (LIF) and contribute to mouse embryonic stem (mES) cell maintenance of pluripotency and self-renewal. In addition, we have shown that fetal bovine serum (FBS) induces Yes auto-phosphorylation and activation. In the present study we confirm that serum also activates TEAD dependent transcription in a time- and dose-dependent manner and we identify Inter-α-inhibitor (IαI) as a component in serum capable of activating the Yes/YAP/TEAD pathway by inducing Yes auto-phosphorylation, YAP nuclear localization and TEAD-dependent transcription. The cleaved heavy chain 2 (HC2) sub-component of IαI, is demonstrated to be responsible for this effect. Moreover, IαI is also shown to efficiently increase expression of TEAD-downstream target genes including well-known stem cell factors Nanog and Oct 3/4. IαI is not produced by the ES cells per se but is added to the cells via the cell culture medium containing serum or serum derived components such as bovine serum albumin (BSA). In conclusion, we describe a novel function of IαI in activating key pluripotency pathways associated with ES cell maintenance and self-renewal.Journal of Biological Chemistry 10/2014; DOI:10.1074/jbc.M114.580076 · 4.60 Impact Factor