title: Increased nuclear stiffness via FAK-ERK1/2 signaling is necessary for synthetic mechano-growth factor E peptide-induced tenocyte migration.
abstract: We have previously reported that a synthetic mechano-growth factor (MGF) C-terminal E-domain with 25 amino acids (MGF-C25E) promotes rat tenocyte migration through the FAK-ERK1/2 signaling pathway. However, the role of the nucleus in MGF-C25E-promoted tenocyte migration and the molecular mechanisms involved remain unclear. In this study, we demonstrate that MGF-C25E increases the Young's modulus of tenocytes through the FAK-ERK1/2 signaling pathway. This increase is not accompanied by an obvious change in the expression of Lamin A/C but is accompanied by significant chromatin condensation, indicating that MGF-C25E-induced chromatin condensation may contribute to the increased nuclear stiffness. Moreover, DNA methylation is observed in MGF-C25E-treated tenocytes. Inhibition of DNA methylation suppresses the elevation in chromatin condensation, in nuclear stiffness, and in tenocyte migration induced by MGF-C25E. The inhibition of the focal adhesion kinase (FAK) or extracellular signal regulated kinase 1/2 (ERK1/2) signals represses MGF-C25E-promoted DNA methylation. It also abolishes chromatin condensation, nuclear stiffness, and cell migration. Taken together, our results suggest that MGF-C25E promotes tenocyte migration by increasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This provides strong evidence for the role of nuclear mechanics in tenocyte migration and new insight into the molecular mechanisms of MGF-promoted tenocyte migration.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Mechanical Science and Engineering, Nagoya University, Nagoya 464-8603, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ju
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Guanbin
authors.initials: G
authors.lastname: Song
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006244:Hardness / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D018625:Microscopy, Atomic Force; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D000072417:Protein Domains; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D000070916:Tenocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: C521108:6-(4-(3-(methylsulfonyl)benzylamino)-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one; D002843:Chromatin; D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D015363:Quinolones; D013450:Sulfones; C519382:mechano-growth factor, rat; D007334:Insulin-Like Growth Factor I; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one