Structure of the Human Protease Nexin Gene and Expression of Recombinant Forms of PN-I

McGrogan, Michael; Kennedy, Jackie; Golini, Fred; Ashton, Nina M.; Dunn, Frances; Bell, Kimberly; Tate, Emily H.; Scott, Randy W.; Simonsen, Christian C.

doi:10.1007/978-1-4684-8357-4_14

Cited by 6 publications

(3 citation statements)

References 28 publications

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“…By contrast, the relative abundance of uPA mRNA, which is also present in epithelial cells of the seminal vesicle (Huarte et al, 1987), was only slightly decreased by castration and was not significantly affected by hormone replacement, indicating that it is probably not under androgen control. As yet only limited information is available on the structure of the PN-I gene (McGrogan et al, 1990), and further studies will be required to determine whether it contains an androgenresponsive element that could allow direct regulation of transcription by the androgen receptor (Beato, 1989). Alternatively, PN-I transcription could be controlled by a trans-acting factor, itself under transcriptional regulation by androgens.…”

Section: Resultsmentioning

confidence: 99%

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

et al. 1993

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A search for inhibitors of urokinase-type plasminogen activator (uPA) in the male and female murine genital tracts revealed high levels of a uPA ligand in the seminal vesicle. This ligand is functionally, biochemically and immunologically indistinguishable from protease-nexin I (PN-I), a serpin ligand of thrombin and uPA previously detected only in mesenchymal cells and astrocytes. A survey of murine tissues indicates that PN-I mRNA is most abundant in seminal vesicles, where it represents 0.2-0.4% of the mRNAs. PN-I is synthesized in the epithelium of the seminal vesicle, as determined by in situ hybridization, and is secreted in the lumen of the gland. PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control.

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Section: Resultsmentioning

confidence: 99%

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

et al. 1993

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“…i-p represent four normal samples: i and j (×6) represent N11; k and l (×10) represent N10; m and n (×10) represent N7; o and p (×20) represent N9. detectable expression of PN1 in healthy fresh foreskin (26). The absence of PN1 expression in situ in healthy dermal fibroblasts and foreskin suggests that in vitro expression seen in cells cultured from healthy skin biopsies is a reflection of the activation seen with culture conditions.…”

Section: Figurementioning

confidence: 96%

A potential role for protease nexin 1 overexpression in the pathogenesis of scleroderma

Strehlow¹,

Jelaska²,

Strehlow³

et al. 1999

J. Clin. Invest.

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Scleroderma currently affects approximately 75,000-100,000 individuals in the United States. Fibroblasts isolated from lesional skin of scleroderma patients overexpress collagens and other matrix components, and this abnormality is maintained for multiple passages in culture. To understand the molecular basis for matrix gene overexpression, we performed a differential display comparison of fibroblasts from clinically lesional and nonlesional scleroderma skin. The results suggested that protease nexin 1 (PN1), a protease inhibitor, is overexpressed in scleroderma fibroblasts. Northern blot verification showed that lesional and nonlesional scleroderma fibroblasts had three-to five-fold increased levels of PN1 mRNA compared with healthy fibroblasts. Western analysis showed that scleroderma fibroblasts also secreted more PN1. In situ hybridization of skin biopsy specimens demonstrated PN1 expression in the dermis of four out of six scleroderma patients but no PN1 expression in the dermis of six healthy volunteers. Transient or stable overexpression of PN1 in mouse 3T3 fibroblasts increased collagen promoter activity or endogenous collagen transcript levels, respectively. PN1 mutagenized at its active site and antisense PN1 both failed to increase collagen promoter activity. These results suggest that overexpression of enzymatically active PN1 may play a pathogenic role in the development of the scleroderma phenotype.

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“…Instead, PI14 is likely to belong to another family formed by PI12 and two other serpin members, PAI1 and PI7. Paradoxically, whereas the solved genomic structures of human and rat PAI1, human PI7, and mouse PI12 revealed the presence of 9 exons and 8 introns (Bosma et al, 1988;Bruzdzinski et al, 1990;McGrogan et al, 1990;Berger et al, 1998), human PI14 was reported to consist of 8 exons and 7 introns (Ozaki et al, 1998). This indicates that PI14 may not have evolved from the same family as did PI12 and the two other serpins.…”

Section: Cdna Sequence and Genomic Structure Of Human Pi14 And Pi12mentioning

confidence: 99%

Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26

Chang

Lin

et al. 2000

Genes Chromosom. Cancer

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Structure of the Human Protease Nexin Gene and Expression of Recombinant Forms of PN-I

Cited by 6 publications

References 28 publications

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle.

A potential role for protease nexin 1 overexpression in the pathogenesis of scleroderma

Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26

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