The University of Chicago

Arch Development Corporation

Margaret M Walsh-Reitz

F Gary Toback

Terence E Martin

Stephen L Gluck

A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease and gastric ulcers.

Control of growth and repair of gastro-intestinal tissues by gastrokines and inhibitors

A novel group of gastrokines called Gastric Antrum Mucosal Protein is characterized. A member of the group is designated AMP-18. AMP-18 genomic DNA, cDNA and the AMP-18 protein are sequenced for human, mouse and pig. The AMP-18 protein and active peptides derived from it are cellular growth factors. Surprisingly, peptides capable of inhibiting the effects of the complete protein, are also derived from the AMP-18 protein. Cytoprotection and control of mammalian gastro-intestinal tissue growth and repair (restitution) is facilitated by the use of the proteins, making the proteins candidates for therapies in inflammatory bowel disease, mucositis, and gastric ulcers.

Novel growth peptides derived from protein factors having molecular weights of about 22 and 45 kDa stimulate mitogenic activity of epithelial, but not fibroblastic cells, in particular, kidney epithelial cells. A source of the factors is scrape-wounded kidney epithelial cells in culture. Synthetic peptides having sixteen amino acids or less, in particular a hexapeptide, YPQGNH (SEQ ID NO: 2) maintain the mitogenic activity. The peptide AQPYPQGNHEASYG (14-Ser) (SEQ ID NO: 15) is effective in reversing acute renal failure in animals. The growth-promoting characteristics of the 22 and 45 kDa proteins and the peptides are useful in treating and diagnosing patients with kidney disease. Nucleotide sequences that encode the factor are useful to develop probes to locate similar factors, to identify genetic disorders involving the factor, and to produce the factor by genetic recombinant methods. The nucleotide sequences and fragments thereof, are also useful for diagnosis and treatment of kidney disorders.

Methods for production of growth-promoting proteins and peptides for kidney epithelial cells

Growth-promoting proteins and peptides for kidney epithelial cells

Autocrine growth factors and isoforms of those factors have been identified, isolated, purified and manipulated. Nucleic acid segments coding for the factors, and antibodies directed to the factors are also aspects of the present invention. The effect of these growth factors on cells is to enhance their growth by increasing mitogenesis. In particular, the growth factors stimulate kidney epithelial cell growth. The growth factors differ from others previously reported in their molecular weights and other properties, for example, resistance to denaturation by dithiothreitol. Methods of preparation and use of the factors are also described. The growth factors are released from kidney epithelial cells by short exposures to a low-sodium environment. The factors have potential for treatment of kidney disease.

Regeneration of kidney tissue and use of autocrine growth factors

Methods and compositions for the preparation and use of autocrine growth

A method of producing autocrine growth factors from kidney epithelial cells by lowering the extracellular sodium concentration. The invention also concerns new growth factors, a method of producing the new growth factors, and the medium used to produce these new growth factors.

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River Forest, IL, United States of America

Margaret M Walsh-Reitz