We evaluated the effect of the conjugate of basic fibroblast growth factor (FGF2) and saporin (FGF2-SAP) on proliferation of cultured keratocytes. Cultured rabbit and human keratocytes were incubated in medium containing 0.01 to 100 nM of chemical conjugate of EGF2 conjugated by disulfide bond to saporin (CCFS1), FGF2 genetically fused to saporin (rFGF2-SAP), FGF2, or saporin for three hours or four days and cell proliferation was quantified four days after the drug treatment. Proliferation of rabbit and human keratocytes was effectively inhibited by three hour and by four day exposure to CCFS1 and rFGF2-SAP in a dose-dependent manner, whereas it was affected minimally by four day exposure to saporin. Their inhibitory effects were detected at concentrations above 0.1 or 1 nM, and were most prominent in serum-stimulated rabbit keratocytes. These results suggest a potential role for FGF2-SAP in limiting proliferation of keratocytes during corneal wound healing.
Animals ; Antineoplastic Agents, Phytogenic/*pharmacology ; Cell Division/drug effects ; Cell Line ; Cells, Cultured ; Corneal Stroma/*cytology/drug effects ; Dose-Response Relationship, Drug ; Fibroblast Growth Factor 2/*pharmacology ; Humans ; Immunotoxins/pharmacology ; *N-Glycosyl Hydrolases ; Plant Proteins/*pharmacology ; Rabbits ; Ribosome Inactivating Proteins, Type 1

The first three disorders discussed are abnormalities of bone: too little bone in cleidocranial dysplasia caused by mutations in RUNX2; too much bone in fibrodysplasia ossificans progressiva with overexpression of BMP4; and abnormal bone in McCune-Albright syndrome and fibrous dysplasia caused by mutations in GNAS1. Disorders of the sonic hedgehog signaling network are discussed next, including holoprosencephaly and the nevoid basal cell carcinoma syndrome, the former being caused by sonic hedgehog (SHH) mutations and the latter being caused by patched mutations (PTCH).
Basal Cell Nevus Syndrome ; genetics ; Craniofacial Abnormalities ; genetics ; Gene Expression Regulation, Developmental ; Holoprosencephaly ; genetics ; Humans ; Mutation