Vascular smooth muscle cell growth factor

Details Vascular smooth muscle cell growth factor Vascular smooth muscle cell growth factor

1998-08-12

2003-02-25

Saoud, Christine J. (Department: 1647)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Peptide containing doai

C514S002600, C530S399000

Reexamination Certificate

active

06525023

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel vascular smooth muscle cell growth factor (VSGF, hereinafter), a DNA encoding the VSGF, a vector comprising the DNA, a transformant obtained by transformation with the vector, and a method for producing the VSGF. Further, the present invention relates to an antibody specifically reacting with the VSGF and a method for producing the antibody. Furthermore, the present invention relates to a wound healing agent containing the VSGF and an agent against abnormal vascular formation.
2. Prior Art
As a factor having vascular smooth muscle cell growth promotion activity, there has been known a fibroblast growth factor [Endocrinology, 118, 82 (1986)], platelet-derived growth factor [Proc. Natl. Acad. Sci. USA, 79, 5867 (1982)], and thrombospondin [Proc. Natl. Acad. Sci. USA, 83, 9050 (198-6)]. Fibroblast growth factor has been known as a factor of abnormal vascular formation [(Proc. Natl, Acad. Sci. USA, 86, 9911 (1989)]. However, these factors have different properties from those of the factor of the present invention.
Although F-spondin has been known as a factor promoting adhesion and elongation of a nerve cell [(Cell, 69, 95 (1992)], an effect of F-spondin on growth of a vascular smooth muscle cell has not been known.
Vascular formation disorders include wound healing failure and intractable skin ulcer, for which no effective drugs are known. In addition, diseases of abnormal vascular formation include diabetic retinopathy, psoriasis, rheumatoid arthritis, angiomatosis, arteriosclerosis, and solid tumor [Science, 235, 442 (1987); Zikken Igaku 8, 369 (1990)]. Fibroblast growth factor has been suggested as related to these diseases. However, an agent for vascular formation disease and particularly, an agent for vascular formation disease caused by the fibroblast growth factor as one of the main factors of vascular formation has not been known.
Furthermore, an antibody specifically reacting to the vascular smooth muscle cell growth factor has not been known so far.
An object of the present invention is to provide a novel vascular smooth muscle cell growth factor promoting growth of vascular smooth muscle cell, a DNA encoding the VSGF, a vector comprising the DNA, a method for producing a transformant obtained by transformation with the vector, a method for producing the VSGF, an antibody specifically reacting to the VSGF and a method of immunological detection by using the antibody.
SUMMARY OF THE INVENTION
The present invention relates to a polypeptide obtained from a mammal and having vascular smooth muscle cell growth promotion activity. The mammal includes bovine and human but are not limited thereto. The present invention relates to a polypeptide having an amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 3, or a polypeptide having vascular smooth muscle cell growth promotion activity and having an amino acid sequence wherein one or more amino acid residues are substituted, deleted, or added in the amino acid sequence represented by SEQ ID NO: 1 or SEQ ID NO: 3, and also relates to a DNA encoding those polypeptides or a DNA having a nucleotide sequence represented by SEQ ID NO: 2 or SEQ ID NO: 4 or a DNA which is hybridizable with the DNA represented by SEQ ID NO:2 or 4 under stringent conditions and encodes a human-derived polypeptide having vascular smooth muscle cell growth promotion activity. Furthermore, the present invention relates to a recombinant vector comprising the VSGF DNA, a transformant obtained by introducing the recombinant vector into a host cell, and a method of producing a polypeptide comprising cultivating a transformant in a culture medium to form and accumulate a polypeptide of the present invention in a culture, and collecting the polypeptide therefrom.
The present invention provides an antibody specifically reacting with the polypeptide of the present invention, a method of producing the antibody, and a method of immunological detection of wound healing failure, intractable skin ulcer, diabetic retinopathy, psoriasis, rheumatoid arthritis, angiomatosis, arteriosclerosis, and solid tumor by using the VSGF antibody of the invention.
The present invention relates to an agent for healing wound or for preventing abnormal vascular formation, containing a polypeptide of the present invention or a polypeptide having an amino acid sequence represented by SEQ ID NO: 5.


REFERENCES:
patent: WO 93/20196 (1993-10-01), None
patent: WO 93/20196 (1993-10-01), None
patent: WO 95/05191 (1995-02-01), None
Science, 235, 442-447 (1987).
Cell, 69, 95-110 (1992).
Proc. Natl. Acad. Sci. USA, 79, 5867-5870 (1982).
Endocrinology, 118, 82 (1986).
Proc. Natl. Acad. Sci. USA, 83, 9050-9054 (1986).
Proc. Natl. Acad. Sci. USA, 86, 9911-9915 (1989).
Klar, A. “F-Spondin: a gene expressed at high levels in the floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension”, Cell, vol. 69, Apr. 3, 1992, PP 95-110.
Nucleotide sequence database EMBL, Id: HS929178; AC H37929 Jul. 27, 1995.
Nucleotide sequence database EMBL, Id: HS449155; AC H09449 Jul. 2, 1995.
Nucleotide sequence database EMBL, Id: HS79392; AC R25793 Apr. 29, 1995.
Nucleotide sequence database EMBL, Id: HD1249630; AC AA449547 Jun. 27, 1995.

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