Combating adaptation to cyclic stretching by prolonging activation of extracellular signal-regulated kinase

Justin S. Weinbaum, Jillian B. Schmidt, Robert T. Tranquillo

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

In developing implantable tissues based on cellular remodeling of a fibrin scaffold, a key indicator of success is high collagen content. Cellular collagen synthesis is stimulated by cyclic stretching but is limited by cellular adaptation. Adaptation is mediated by deactivation of extracellular signal-regulated kinase (ERK); therefore inhibition of ERK deactivation should improve mechanically stimulated collagen production and accelerate the development of strong engineered tissues. The hypothesis of this study is that p38 mitogen activated protein kinase (p38) activation by stretching limits ERK activation and that chemical inhibition of p38 α/γ isoforms with SB203580 will increase stretching-induced ERK activation and collagen production. Both p38 and ERK were activated by 15 min of stretching but only p38 remained active after 1 h. After an effective dose of inhibitor was identified using cell monolayers, 5 μM SB203580 was found to increase ERK activation by two-fold in cyclically stretched fibrin-based tissue constructs. When 5 μM SB203580 was added to the culture medium of constructs exposed to 3 weeks of incremental amplitude cyclic stretch, 2.6 fold higher stretching-induced total collagen was obtained. In conclusion, SB203580 circumvents adaptation to stretching induced collagen production and may be useful in engineering tissues where mechanical strength is a priority.

Original languageEnglish (US)
Pages (from-to)279-286
Number of pages8
JournalCellular and Molecular Bioengineering
Volume6
Issue number3
DOIs
StatePublished - Sep 1 2013

Fingerprint

Collagen
Extracellular Signal-Regulated MAP Kinases
Stretching
Activation
Chemical activation
p38 Mitogen-Activated Protein Kinases
Tissue
Fibrin
Fold
Tissue Engineering
Protein Kinase
Remodeling
Scaffold
Scaffolds (biology)
Stretch
Tissue engineering
Scaffolds
Inhibitor
Accelerate
Strength of materials

Keywords

  • Cell signaling
  • Collagen
  • Fibrin
  • Fibroblast
  • Inhibition
  • Mechanical signaling
  • Mitogen-activated protein kinase
  • P38.

Cite this

Combating adaptation to cyclic stretching by prolonging activation of extracellular signal-regulated kinase. / Weinbaum, Justin S.; Schmidt, Jillian B.; Tranquillo, Robert T.

In: Cellular and Molecular Bioengineering, Vol. 6, No. 3, 01.09.2013, p. 279-286.

Research output: Contribution to journalArticle

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