Response of Human Renal Cell Carcinoma Cells to Bone Morphogenetic Proteins, and the Expression of Bone Morphogenetic Protein Receptors / 대한비뇨기과학회지

PURPOSE: Bone morphogenetic protein (BMP) is a pleiotropic growth factor, which has been suggested to play a critical role during the development and homeostasis of the kidney. We evaluated the response of the human renal cell carcinoma (RCC) cell lines to BMPs. MATERIALS AND METHODS: We evaluated the growth rate of the human RCC cell lines, 112, 117 and 181, according to the concentrations of BMP-4, -6 and -7, and detected the levels of the BMP receptors (BMPRs) expressed in the cell lines. To demonstrate that the defect in BMP-6 signaling is at the receptor level, BMP-6 resistant cell lines were transfected, with adenovirus containing the constitutively active form of the BMP receptor types II (BMPR-II). After transfection, the cells were transfected with pSBE4, the construct of the BMP-6-responsive luciferase reporter gene, and a luciferase assay performed. RESULTS: The BMP-6 inhibited the proliferation of the 112, but not those of the 117 and 181 cells, in a dose-dependent manner. From Northern blot and immunoblot analyses, it was demonstrated that the 117 and 181 cells had undetectable levels of BMPR-II expression. The levels of luciferase activity, following adenovirus infections, was elevated in both the 117 and 181 cells, suggesting that the down-stream signaling molecules of the BMP-6 was intact in these cell lines. CONCLUSIONS: Taken together, these results demonstrate that the human RCC cell lines 117 and 181 are resistant to the growth inhibitory effects of the BMP-6 due to their decreased levels of BMPR-II expression.

Comparison of bone morphogenetic protein receptors expression in the fetal and adult skin

Wounds on fetal skin can be repaired without leaving scars until the second trimester, but after this period, skin wounds leave scars as in adults. It's known that certain growth factors such as TGF-beta, and bFGF are present at a very low levels during wound repair in fetal skin. These low levels of growth factors minimize inflammatory response and fibroblast proliferation at the wound site, which in turn inhibit collagen synthesis, and thus, allows scarless wound healing. Recently bone morphogenetic proteins (BMPs), one of the TGF-beta superfamily members, have been studied in the wound healing process. According to several studies, BMPs are related to the differentiation and growth of epithelial and mesenchymal cells, but the precise functions of BMPs and of BMP receptors on skin wound healing have not been elucidated. In this study, we investigated the expression pattern of BMP receptors in fetal skin during the second trimester and in adult skin by immunohistochemical staining and RT-PCR. BMP receptors were detected on the suprabasal epithelial cells and in the hair follicles in adult skin, but were not defected in the fetal skin except for the hair follicles. This was confirmed by confirming mRNA levels of BMP receptors by RT-PCR in both adult and fetal skins. In conclusion, BMPs and BMP receptors seem to be related to fetal and adult wound healing, and low levels of BMPs and BMP receptors during the second trimester seem to contribute to scarless wound healing in the fetus, as is TGF-beta during the second trimester.