Silibinin's regulation of proliferation and collagen gene expressions of rat pancreatic β-cells cultured on types I and V collagen involves β-catenin nuclear translocation.
Extracellular matrix (ECM) molecules have multiple functions; prevention of cytotoxicity, provision of mechanical support, cell adhesive substrates and structural integrity in addition to mediation of cellular signaling. In this study, we report that the proliferation of INS-1 cells cultured on collagen I-coated dishes is enhanced, but it is inhibited on collagen V-coated dishes. Inhibitory proliferation on collagen V-coated is not due to apoptosis induction. Silibinin decreases hepatic glucose production and protects pancreatic β-cells, as a potential medicine for type II diabetes. Silibinin up-regulates the proliferation of cells cultured on both collagen I- and V-coated dishes. Collagen-coating regulates gene expression of collagen in a collagen type-related manner. Silibinin increases mRNA expression of collagen I in the cells on collagen I- and V-coated dishes; however, silibinin decreases collagen V mRNA expression on collagen I- and V-coated dishes. Collagen I-coating significantly enhances nuclear translocation of β-catenin, while collagen V-coating reduces it. Differential effects of silibinin on collagen I mRNA and collagen V mRNA can be accounted for by the finding that silibinin enhances nuclear translocation of β-catenin on both collagen I- and V-coated dishes, since phenomenologically nuclear translocation of β-catenin enhances collagen I mRNA but represses collagen V mRNA. These results demonstrate that nuclear translocation of β-catenin up-regulates proliferation and collagen I gene expression, whereas it down-regulates collagen V gene expression of INS-1 cells. Differential gene expressions of collagen I and V by nuclear β-catenin could be important for understanding fibrosis where collagen I and V may have differential effects.
['Yang|Jing|J|', 'Sun|Yue|Y|', 'Liu|Xiaoling|X|', 'Xu|Fanxing|F|', 'Liu|Weiwei|W|', 'Hayashi|Toshihiko|T|', 'Imamura|Yasutada|Y|', 'Mizuno|Kazunori|K|', 'Hattori|Shunji|S|', 'Tanaka|Keisuke|K|', 'Fujisaki|Hitomi|H|', 'Tashiro|Shin-Ichi|SI|', 'Onodera|Satoshi|S|', 'Ikejima|Takashi|T|']
D000818:Animals D002417:Cattle D002467:Cell Nucleus D049109:Cell Proliferation D024042:Collagen Type I D024062:Collagen Type V D005786:Gene Expression Regulation D050417:Insulin-Secreting Cells D021381:Protein Transport D012333:RNA, Messenger D051381:Rats D000077385:Silybin D051176:beta Catenin
silibinin proliferation β-catenin INS-1 cells Collagen type I collagen type V