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Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro
Chee Ping Ng1, Boris Hinz, Melody A Swartz
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, 633 Clark Street, Chicago, IL 60208, USA.
Journal of Cell Science
|September 29, 2005
Summary
Interstitial fluid flow, not just biochemical signals, drives fibroblast differentiation into myofibroblasts. This process, crucial for wound healing and fibrosis, is mediated by TGF-beta1 and alpha1beta1 integrin, highlighting the role of the biophysical environment.
Area of Science:
- Biophysics
- Cell Biology
- Tissue Engineering
Background:
- Fibroblast differentiation into alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblasts is key to wound healing, scarring, and fibrosis.
- Transforming growth factor beta1 (TGF-beta1) is a known mediator of myofibroblast differentiation, often released during inflammation.
- The biophysical environment, including interstitial fluid flow, may also influence these processes.
Purpose of the Study:
- To investigate the role of interstitial fluid flow in fibroblast differentiation and extracellular matrix remodeling.
- To determine if biophysical forces alone can induce myofibroblast differentiation and collagen alignment.
- To elucidate the molecular mechanisms, including TGF-beta1 and integrin involvement, underlying flow-induced fibroblast responses.
Main Methods:
- 3D cell culture models to simulate interstitial flow.
- Assessment of alpha-SMA expression to quantify myofibroblast differentiation.
- Analysis of collagen alignment and fibroblast proliferation.
- Use of TGF-beta1 blocking antibodies and alpha1beta1 integrin inhibition.
Main Results:
- Low levels of interstitial (3D) flow induced fibroblast-to-myofibroblast differentiation, collagen alignment, and proliferation without exogenous mediators.
- These flow-induced effects were associated with TGF-beta1 induction and could be blocked by TGF-beta1 antibodies.
- alpha1beta1 integrin inhibition prevented flow-induced differentiation and collagen alignment but not gel contraction.
Conclusions:
- The biophysical environment, specifically interstitial fluid flow, is a significant driver of fibroblast differentiation and fibrogenesis.
- Interstitial flow can initiate fibrotic processes independently of, or in conjunction with, biochemical mediators like TGF-beta1.
- Targeting interstitial flow or its mediators may offer novel therapeutic strategies for fibrotic diseases.