[Synergistic effect of monocyte chemotactic protein-1 and aristolochic acid I on transdifferentiation of human tubular epithelial cells in vitro].Zhonghua Nei Ke Za Zhi. 2000 Dec; 39(12):831-4.ZN
To test the possible role of monocyte chemotactic protein-1 (MCP-1) and its synergistic effect with aristolochic acid I (AAI) on tubular epithelial-myofibroblast transdifferentiation (TEMT) of human renal tubular epithelial cells (HKC) in vitro.
The cultured HKC cells were divided into four groups: (1) negative control (serum-free); (2) MCP-1 group; (3) AAI group; (4) AAI + MCP-1 group. The expression of alpha-smooth muscle actin (alpha-SMA), vimentin and cytocreatin was assessed by indirect enzyme immunohistochemistry and the percentages of alpha-SMA((+)) HKC cells were assessed by flow cytometry.
The expression of cytocreatin of HKC cells decreased, while the expression of alpha-SMA, vimentin increased when treated with MCP-1 or with AAI and MCP-I concomitantly. Alpha-SMA((+)) HKC cells cultured in serum-free medium was 3.1% by flow cytometry. The percentages of alpha-SMA((+)) HKC cells were 8.6%, 9.6%, 13.4% (P < 0.05 vs control) when treated with 20, 40, 80 microg/L of AAI. The percentages of alpha-SMA((+)) HKC cells were 0.5% and 1.4% (P > 0.05 vs control) when treated with 5, 10 microg/L. The percentages of alpha-SMA((+)) HKC cells were 20%, 26.2%, 20.3%, 23.2% (P < 0.05 vs control) when treated with 0.001, 0.01, 0.05, 0.1 microg/L of MCP-1. When the HKC cells were treated with MCP-1 (0.1 microg/L) and AAI (5, 10, 20, 40 microg/L), the percentage of alpha-SMA((+)) cells increased markedly to 23.2%, 98.7%, 81.5%, 65.1% (P < 0. 01 vs group 1, 2, 3, respectively).
These findings suggest that: (1) MCP-1 may induce the transdifferentiation of HKC cells into myofibroblasts in vitro; (2) AAI at some doses may partially induce HKC cells transdifferentiation. (3) MCP-1 and AAI may have a synergistic effect on transdifferentiation of HKC cells in vitro.