F. Gary Toback, M.D., Ph.D.

Autocrine Growth Factors that Mediate Regeneration After Renal and GI Epithelial Cell Injury

Research Summary

Work in this laboratory is focused on defining the factors that regulate growth of kidney epithelial cells and identifying the molecular mechanisms by which they act. Four projects are currently underway. 1) For more than a decade we have searched for mechanisms by which systemic K deficiency induces renal growth. Current research employs a tissue culture model in which a reduction of the K concentration of the medium initiates accelerated growth in nontransformed monkey kidney epithelial cells of the BSC-1 line. 2) We found that the nucleotide adenosine disphosphate (ADP) is the most potent mitogen yet defined for BSC-1 cells. ADP activates expression of early growth response genes and induces release of platelet-derived growth factor BB which appears to act in a paracrine manner. We are isolating and characterizing a novel autocrine growth factor released by BSC-1 cells exposed to ADP and defining cytoskeletal changes that occur during the onset of mitogenesis. 3) In 1986 we reported that BSC-1 cells exposed to a reduction in the sodium concentration of the medium released autocrine growth factors. Recently, a reversed-phase HPLC procedure was developed to isolate microgram amounts of growth factor protein. Studies are underway to obtain amino acid sequence information, develop an antiserum, and use the information to obtain cDNA clones to determine its nucleotide sequence. 4) We plan to define the mechanisms by which Ca oxalate monohydrate crystals stimulate growth of renal epithelial cells.

Selected Papers

Martin TE, Powell CT, Wang Z, Bhattacharya S, Walsh-Reitz MM, Agarwal K, and Toback FG. (2003). A novel mitogenic protein that is highly expressed in cells of the gastric antrum mucosa. American Journal of Physiology 285: G332-G343.

Toback FG, Walsh-Reitz MM, Musch MW, Chang EB, Del Valle J, Ren H, Huang E, and Martin TE.  (2003). Peptide fragments of AMP-18, a novel secreted gastric anrum mucosal protein, are mitogenic and motogenic. American journal of Physiology 285: G344-G353.

Kumar V, Yu S, Farell G, Toback FG, and Lieske JC.  (2004). Renal epithelial cells constitutively produce a protein than blocks adhesion of crystals to their surface. American Journal of Physiology 287: F373-F383.

Walsh-Reitz, M.M., E.F. Huang, M.W. Musch, E.B. Chang, T.E. Martin, S. Kartha, and Toback FG. (2005). AMP-18 protects barrier function of colonic epithelial cells: role of tight junction proteins. American Journal of Physiology. 289:G163-G171.