Disease relevance of Serpine2

• The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies [1].
• These results suggest that thrombin may be involved in the progression of muscular dystrophy or the regeneration of muscle fibers after the onset of the disease and that the reduced level of PN-1 may enhance the activities stimulate the activities of muscle proteases, including dystrypsin, at a preclinical stage in mdx mice [2].
• Since the experiments were planned in order to exclude the presence of protease-nexin in the incubation medium, these data suggest the existence of a plasminogen-independent novel receptor for the catalytic site of plasminogen activators, the number on the cell surface of which decreases in Rous sarcoma virus-transformed mouse fibroblasts [3].
• Neurite outgrowth activity of protease nexin-1 on neuroblastoma cells requires thrombin inhibition [4].

Psychiatry related information on Serpine2

• Absence of PN-1 results in altered semen protein composition, which leads to inadequate semen coagulation and deficient vaginal plug formation upon copulation [5].

High impact information on Serpine2

• Binding of thrombin-protease nexin to cells is mediated by the protease nexin portion of the complex to a high-affinity cellular binding site [6].
• As thrombin is a potent mitogen for a variety of fibroblast-like cells in culture, we examined whether protease nexin itself regulates thrombin-stimulated cell division [6].
• Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle [7].
• Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1 [5].
• Furthermore, a naturally occurring serine protease inhibitor, protease nexin I (PNI), which closely colocalizes with acetylcholine receptors at the neuromuscular junction, inhibited the synapse reduction at the same low concentration [8].

Biological context of Serpine2

• Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development [9].
• This distinct pattern appears identical in the genomic structures of human plasminogen activator inhibitor-1 (PAI1) at 7q21 and protease nexin 1 (PI7) at 2q33-35, confirming that these four genes in three different chromosomes form a discrete subset within the serpin superfamily [10].
• Transgenic embryos expressing the bacterial lacZ gene under the control of different fragments of the PN-1 upstream regulatory region were used to demarcate an enhancer sufficient for expression at this putative segmental border [11].
• Variable and multiple expression of Protease Nexin-1 during mouse organogenesis and nervous system development [12].
• Compensatory changes in GABA-mediated inhibition in Thy 1/PN-1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic transmission [13].

Anatomical context of Serpine2

• Consistent with these findings, abnormal PN-1 expression was found in the semen of men displaying seminal dysfunction [5].
• In the embryonic spinal cord, PN-1 expression occurs in cells lining the neural canal that are different from the cells previously shown to express tPA [12].
• In adults, few distinct neuronal cell populations like pyramidal cells of the layer V in the neocortex retained detectable levels of PN-1 expression [12].
• These findings suggest a role for PN-1 in the maturation of the central nervous system, a phase that is accompanied by the appearance of different forms of PN-1 [12].
• These analyses revealed distinct temporal and spatial PN-1 expression patterns in developing cartilage, lung, skin, urogenital tract, and central and peripheral nervous system [12].

Associations of Serpine2 with chemical compounds

• Localization of protease nexin-1 gene Spi4 between villin and acetylcholine receptor gamma genes on mouse Chromosome 1 [14].
• By inhibiting endocytosis with phenylarsine oxide, which does not affect cellular binding of Th-PN complexes, we showed that complexes must be internalized before they are degraded [15].
• Because PN has a heparin-binding site, this indicates that protease-PN complexes might bind to a cellular heparin-like site [15].
• Production of both PN (by HF cells and WI-26 cells) and the cytoplasmic factor (by HF cells and 3T3 cells) are stimulated by epidermal growth factor and phorbol myristate acetate [16].
• The cells transfected with the oligopurine variant displayed morphological changes, upregulation of major histocompatibility complex I, and increased expression of protease nexin I. Dramatic inhibition of tumor growth occurred in nude mice following injection of transfected C6 cells [17].

Physical interactions of Serpine2

• A Krox binding site regulates protease nexin-1 promoter activity in embryonic heart, cartilage and parts of the nervous system [18].

Regulatory relationships of Serpine2

• 5. These results suggest that Krox factors are among the important transcription factors regulating protease nexin-1 expression and thereby intracellular proteolytic activity in embryonic heart, cartilage and parts of the nervous system [18].
• We propose that protease nexin 1 inhibits the destruction of myotube matrix by inactivating the plasmin/plasminogen activation system and may be the physiologic regulator of this system during muscle development in vivo [19].

Other interactions of Serpine2

• In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis [1].
• To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions [1].
• Expression of mRNA for plasminogen activators and protease nexin-1 in innervated and denervated mouse skeletal muscle [20].
• Regulation of prothrombin, thrombin receptor, and protease nexin-1 expression during development and after denervation in muscle [21].
• Among the 24 genes tested, the calcium channel subunits alpha1B and alpha1C, the protease Nexin 1, and the calcium-binding protein calbindin were differentially expressed in adult SC and CC cells and the potassium channel subunit Kv4.3 was expressed preferentially in CC cells at both stages of development [22].

Analytical, diagnostic and therapeutic context of Serpine2

• Since protease nexin I (PNI), a serpin homologous with CrmA, prevents apoptosis of lumbar motor neurons and is increased after nerve injury, we examined mRNA by RT-PCR for PNI expression [23].

References