Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues
Patent
1994-04-19
1999-01-12
Ulm, John
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
530328, 530329, 530330, 530395, 530412, 530413, 435325, 435375, 536 235, C07K 14475, C12N 1512
Patent
active
058591923
DESCRIPTION:
BRIEF SUMMARY
This application is the U.S. national phase of PCT/FR92/00867 filed Sep. 16, 1992.
A subject of the invention is proteins which, in particular, are capable of constituting factors for cellular functional regulation and their biological applications.
The fundamental role of interactions and communications between cells is known.
Cell-cell interactions assume a major importance in the development and organisation of multicellular organisms, as well as in their physiology and their pathology.
It is generally accepted that these interactions take place due to the effect of circulating soluble factors, but also by means of cell adhesion molecules (CAM), matrix support adhesion molecules and molecules constituting functional structures between the cells.
These molecules provide at the same time, regulation of genesis during the early stages of development, including moreover the primary processes such as cellular proliferation and migrations. They give rise to signals which lead to differential expression of genes and in this way, to embryonic induction (see in particular Gallin et al., Proc. Natl. Acad. Sci. USA. 83:8235-8239, 1986; Edelman, Immunol. Rev. 100:11-45, 1987; Jessel, Neuron. 1:3-13, 1988). Although the role of these molecules has been well established, the molecular mechanisms involved in these coordinated regulations are however still largely unexplained.
The communications between cells also play an important role in maintaining the differential expression of genes of mature cells of adult tissues, as has been shown in particular in work carried out on the peripheral and central nervous systems (see, in particular, Rathjen et al., J. Cell. Biol. 104:343-353, 1987 and Seilheimer et al., J. Cell. Biol. 109: 3095-3103, 1989). Another example of great interest in this respect is provided by the adult liver. In fact, it is noted that the dissociation of hepatic tissue in order to isolate the hepatocytes leads to a strong reduction of the transcription of genes coding for the specific functions of the liver (see Clayton et al. Mol. Cell. Biol. 5:2623-2632, 1985). In addition, it was noted that the establishment of homotypic interactions in culture, i.e. between hepatocytes, does not permit the preservation of their adult phenotype, while the proteoglycans induce the formation of functional junctional structures and restore the transcription of specific mRNA's in primary cultures. These results taken together tend to demonstrate the major role of non-parenchymatous cells on the differential transcription of specific genes of the liver in adult hepatocytes.
Some of the co-inventors of the present Application have described in the Patent FR 8307148 of 29th Apr. 1983, in the name of INSERM, a process for the co-culture of adult human hepatocytes with a heterologous cell population, but of hepatic origin. During the co-culture, the establishment of contacts between the two cell populations was noted. It follows that the functional activities of the hepatocytes were maintained over several weeks. During the co-culture, the secretion and deposition of various components of a matrix was observed giving a complex extracellular matrix network which surrounds and covers the hepatocyte colonies and in a parallel and coordinated manner, activation of the expression of specific genes of the liver.
The inventors have used this system of the co-culture of hepatocytes to study the causal relationships between the different biological events which lead to a stable differentiation of hepatocytes in the adult liver.
An immunological approach to this problem allowed them, by using a determined monoclonal antibody, to reveal the critical role played in this respect by a membrane protein.
In pursuing this work, the inventors noted that cells other than hepatocytes, in tissues other than liver tissues, contained in their membrane proteins of this type which are also recognised by the monoclonal antibody in question.
Therefore an aim of the invention is to provide proteins which are involved in a major way in the interactions
REFERENCES:
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Tingstroem et al, "Distribution and Dynamics of Cell Surface-Associated CellCAM 105 in Cultured Rat Hepatocytes", Chemical Abstracts 112(5):392, abstract No. 33895e (1990).
Hopf et al, "Glycoproteins of Rat Liver Plasma Membranes: Their Hepatocellular, Intestinal and Renal Expression in Rat, Rabbit and Human", Chemical Abstracts 114(19):503, abstract No. 182615g (1991).
Baffet et al, "Distinct Effects of Cell-Cell Communication and Corticosteroids on the Synthesis and Distribution of Cytokeratins in Cultured Rat Hepatocytes", Biological Abstracts 92(9):AB-291, abstract No. 97586 (1991).
Fraslin et al, "Dependence of Hepatocyte-Specific Gene Expression on Cell-Cell Interactions in Primary Culture", Chemical Abstracts 104(5):395, abstract No. 32390j (1986).
Gallin et al, "Antibodies to liver cell adhesion molecular perturb inductive interactions and alter feather pattern and structure", Proc. Natl. Acad. Sci. USA 83:8235-8239 (1986).
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Corlu Anne
Guillouzo Christiane
Kneip Bernard
Cabinet Armengaud Aine
Mertz Prema
Ulm John
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