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.

Abstract

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.

• Authors: Jing Yang, Yue Sun, Xiaoling Liu, Fanxing Xu, Weiwei Liu, Toshihiko Hayashi, Yasutada Imamura, Kazunori Mizuno, Shunji Hattori, Keisuke Tanaka, Hitomi Fujisaki, Shin-Ichi Tashiro, Satoshi Onodera, Takashi Ikejima
• Journal: Connective tissue research (Connect Tissue Res) Vol. 60 Issue 5 Pg. 463-476 (09 2019) ISSN: 1607-8438 [Electronic] England
• PMID: 30871385 (Publication Type: Journal Article)

Chemical References

• Collagen Type I
• Collagen Type V
• RNA, Messenger
• beta Catenin
• Silybin

Topics

• Animals
• Cattle
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects, genetics)
• Collagen Type I (genetics, metabolism, pharmacology)
• Collagen Type V (genetics, metabolism, pharmacology)
• Gene Expression Regulation (drug effects)
• Insulin-Secreting Cells (drug effects, metabolism)
• Protein Transport (drug effects)
• RNA, Messenger (genetics, metabolism)
• Rats
• Silybin (pharmacology)
• beta Catenin (metabolism)