The influence of synthetic peptides derived from the laminin alpha1 chain on hepatocyte adhesion and gene expression.
Laminin-111, a heterotrimer composed of the laminin alpha1, beta1, and gamma1 chains, has been used as a biomaterial for primary cell culture to maintain cellular functions. Our previous studies have reported that synthetic peptides derived from laminin alpha1 exhibit biological functions such as influencing cell adhesion, migration, angiogenesis, and tumor metastasis. In this study we screened hepatocyte attachment peptides using twenty-five biologically active peptides from laminin alpha1 and examined the maintenance of hepatic function on the peptides using primary rat hepatocytes. Peptide A13 (RQVFQVAYIIIKA), mouse laminin alpha1 chain residues 121-133, exhibited the strongest activity. Furthermore, primary hepatocytes on A13 peptide maintained expression of hepatic differentiation markers such as tyrosine aminotransferase, tryptophan-2,3-dioxygenase, and cytochrome P450. We also determined the active core sequence of A13 using systematically truncated N- and C-terminal peptides. The results indicated that the nine-amino acid sequence RQVFQVAYI was critical for A13's hepatocyte adhesion activity. However, the truncated peptides could not interact with beta1-intgerin and maintain expression of hepatic differentiation markers. The amino acid sequence of A13 peptide was required for regulating hepatocyte behavior. The hepatocyte adhesive peptides can be utilized in tailoring synthetic biomaterials in order to achieve a specific cellular response.
Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Hachioji, Tokyo 192-0392, Japan. kikkawa@toyaku.ac.jp
Yamato
Y
Kikkawa
Naoya
N
Takahashi
Yuji
Y
Matsuda
Takahiro
T
Miwa
Taneyasu
T
Akizuki
Akira
A
Kataoka
Motoyoshi
M
Nomizu
D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002614:Chelating Agents / Q000378:metabolism; D004492:Edetic Acid / Q000378:metabolism; D015870:Gene Expression; D006493:Heparin / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000502:physiology*; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002614:Chelating Agents; D019012:Integrin beta1; D007797:Laminin; D010455:Peptides; D020033:Protein Isoforms; C084098:laminin A; D006493:Heparin; D004492:Edetic Acid