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Evidence that filopodia outgrowth is a common final pathway for fibroblast growth inhibition in vitro
B M Stanulis-Praeger1, M Yaar, B A Gilchrest
1USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
Abstract:
To identify events associated with fibroblast growth inhibition, the effect of two known inhibitors, interferon-alpha and all-trans retinoic acid, on the growth and surface morphology of cultured fibroblasts was examined. Interferon-alpha administered at seeding reduced both growth rate and saturation density; all-trans retinoic acid reduced only saturation density. However, both negative growth modulators were associated with an increase in filopodia outgrowth and an increase in intracellular filamentous actin in a time course corresponding to onset of growth inhibition by these agents. In combination with earlier findings, these data suggested that, regardless of etiology, cultured fibroblast growth restriction is mediated in part by an actin-dependent outgrowth of filopodia that augment intercellular contact.
Insights
Fibroblast growth inhibitors, interferon-alpha and all-trans retinoic acid, increase cell-cell contact via actin-dependent filopodia outgrowth. This suggests a mechanism for fibroblast growth restriction regardless of cause.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Fibroblast growth is crucial for tissue repair and development.
- Understanding fibroblast growth regulation is key to treating fibrotic diseases.
Purpose of the Study:
- To investigate the cellular events associated with fibroblast growth inhibition.
- To examine the effects of interferon-alpha and all-trans retinoic acid on fibroblast morphology and growth.
Main Methods:
- Cultured fibroblasts were treated with interferon-alpha or all-trans retinoic acid.
- Cell growth rate, saturation density, and surface morphology were analyzed.
- Intracellular filamentous actin and filopodia outgrowth were quantified over time.
Main Results:
- Interferon-alpha reduced both fibroblast growth rate and saturation density.
- All-trans retinoic acid reduced only fibroblast saturation density.
- Both inhibitors increased filopodia outgrowth and intracellular filamentous actin, correlating with growth inhibition.
Conclusions:
- Fibroblast growth restriction involves actin-dependent filopodia outgrowth.
- Increased filopodia augment intercellular contact, contributing to growth inhibition.
- This mechanism may be common across different causes of fibroblast growth restriction.