Human ADAMTS-1 protein, gene encoding the same, pharmaceutical composition, and method for immunologically analyzing human ADAMTS-1 protein

Abstract

A human ADAMTS-1 protein, a gene encoding the same, a pharmaceutical composition containing the protein as an active ingredient, and a method for immunologically analyzing the human ADAMTS-1 protein are disclosed. The protein can decrease the number of leukocytes and platelets, and at the same time, increase the number of erythrocytes.

Description

[0001] The present invention relates to a human ADAMTS-1 protein, a gene encoding the same, a pharmaceutical composition, and a method for immunologically analyzing the human ADAMTS-1 protein.[0002] A mouse ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs)-1 gene has been cloned as a cDNA from a mouse colon cancer cell which induces cancer cachexia when transplanted to a mouse. The mouse ADAMTS-1 protein encoded by the gene is a unique protein containing a matrix metalloproteinase domain, a disintegrin domain, and three thrombospondin domains [J. Biol. Chem., 272, 556-562 (1997)]. The physiological functions of the mouse ADAMTS-1 protein has not been reported, but there have been reports of each individual functional domain contained therein.[0003] For example, a snake venom disintegrin belongs to a family of proteins which are rich in cystein, and exhibit an anticoagulant activity [Semin. Hematol., 31, 289-300 (1994)].[0004] Further, for example, an ADAM (A di...

AI Technical Summary

Benefits of technology

[0069] If a DNA fragment containing a desired gene is directly introduced into a host cell, the fragment is not reproduced. However, an extrachromosomal gene reproducible in a cell, such as a plasmid, may be used as a vector to prepare an expression plasmid. A vector which may be used preferably contains genetic information necessary for replication in a host cell, can be independently replicated, is easily isolated and purified from a host cell, and contains a detectable marker.

[0092] It is generally known that, when inflammation occurs, leukocytes are activated in blood, move to an inflamed site, evolute and / or cause pathosis. Therefore, it is believed that the human ADAMTS-1 protein of the present invention would be effective in the treatment of various inflammatory diseases, such as rheumatic arthritis, psoriasis, asthma, hepatitis, Kawasaki disease, gout, adult respiratory distress syndrome (ARDS), Crohn's disease, ulcerative colitis, sepsis, or nephritis. Further, the human ADAMTS-1 protein of the present invention exhibits a function to decrease the number of leukocytes and platelets, and thus would be effective in a treatment of true hypervolemia. The human ADAMTS-1 protein of the present invention exhibits a function to decrease the number of platelets. Therefore, it is believed that the human ADAMTS-1 protein of the present invention would exhibit an anti-thrombotic action, and would be effective in the treatment of cardiac infarction, cerebral inferction, or multi-organ failure. The human ADAMTS-1 protein of the present invention exhibits a function to significantly increase the number of erythrocytes, and would be effective in a treatment of anemia, as erythropoietin.

[0104] In the analysis step of the human ADAMTS-1 protein in the sample, the sample is first brought into contact with the substance immunologically reactive to the human ADAMTS-1 protein. If the sample does not contain the human ADAMTS-1 protein, a reaction with the immunologically reactive substance does not occur. If the sample contains the human ADAMTS-1 protein, the immunologically reactive substance binds the human ADAMTS-1 protein, and a complex of the immunologically reactive substance and the human ADAMTS-1 protein is formed in an amount correlated with that of the human ADAMTS-1 protein present in the sample. The complex may be easily detected by a known method, and therefore, an existence of the human ADAMTS-1 protein in the sample can be detected by detecting the existence of the complex, or an amount of the human ADAMTS-1 protein in the sample can be measured by measuring the amount of the complex. The human ADAMTS-1 protein in a tissue or a cell may be measured, using a tissue section sample or a cell sample in a fluorescent antibody technique or an enzyme antibody technique.

[0124] The polynucleotide contains a sequence complementary or substantially complementary to that of a part of the mRNA transcribed from a selected gene (DNA), and thus forms a double strand with the mRNA transcribed from the target gene. It is believed that any polynucleotide sufficiently complementary to form a stable complex with a target mRNA can be used. The polynucleotide able to be used in the present invention may be complementary to substantially any region in a target mRNA. The polynucleotide can be used as a DNA probe for detecting an increase or a decrease of expression of the mRNA specific to the human ADAMTS-1 protein gene. That is, the polynucleotide is specifically attached to the mRNA of the target human ADAMTS-1 protein, and forms a molecular hybrid, whereby a degree of expression of the human ADAMTS-1 protein in cells can be detected.

Problems solved by technology

However, little have been known about the physiological roles of these ADAM family proteins.

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