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Extracellular matrix regulation of fibroblast function: redefining our perspective on skin aging

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Journal of Cell Communication and Signaling Aims and scope

Abstract

The dermal extracellular matrix (ECM) comprises the bulk of skin and confers strength and resiliency. In young skin, fibroblasts produce and adhere to the dermal ECM, which is composed primarily of type I collagen fibrils. Adherence allows fibroblasts to spread and exert mechanical force on the surrounding ECM. In this state, fibroblasts display a “youthful” phenotype characterized by maintenance of the composition and structural organization of the dermal ECM. During aging, fibroblast-ECM interactions become disrupted due to fragmentation of collagen fibrils. This disruption causes loss of fibroblast spreading and mechanical force, which inextricably lead to an “aged” phenotype; fibroblasts synthesize less ECM proteins and more matrix-degrading metalloproteinases. This imbalance of ECM homeostasis further drives collagen fibril fragmentation in a self-perpetuating cycle. This article summarizes age-related changes in the dermal ECM and the mechanisms by which these changes alter the interplay between fibroblasts and their extracellular matrix microenvironment that drive the aging process in human skin.

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Abbreviations

UV:

ultraviolet

ECM:

extracellular matrix

GAG:

glycoseaminoglycan

PG:

prostaglandin

Lys:

lysine

Hyl:

hydroxylysine

LOX:

lysyl oxidase

MMP:

matrix metalloprotease

ROS:

reactive oxygen species

PTP:

protein tyrosine phosphatase

RTK:

receptor tyrosine kinase

MAPK:

mitogen activated protein kinase

ERK:

extracellular signal-regulated kinase

JNK:

c-Jun N-terminal kinase

AP-1:

activated protein 1

CCN1:

cysteine-rich protein 61

TNF- α:

tumor necrosis factor alpha

TGF- β:

transforming growth factor beta

GzmB:

granzyme B

AADM:

age-associated dermal microenvironment

IGFBP:

insulin-like growth factor binding protein

VWC:

von Willebrand factor type C

TSP1:

thrombospondin type 1

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Acknowledgements

This work was supported by funding from the National Institute of Health (grant R01-AG051849 and RO1-AG054835 to GJF and TQ and T32-AM07197 to MAC – PI: JT Elder).

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Authors and Affiliations

  1. Department of Dermatology, University of Michigan Medical School, 1301 Catherine, Medical Science I, Room 6447, Ann Arbor, MI, 48109-5609, USA

    Megan A. Cole, Taihao Quan, John J. Voorhees & Gary J. Fisher

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  1. Megan A. Cole
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  2. Taihao Quan
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  3. John J. Voorhees
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  4. Gary J. Fisher
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Correspondence to Gary J. Fisher.

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Cole, M.A., Quan, T., Voorhees, J.J. et al. Extracellular matrix regulation of fibroblast function: redefining our perspective on skin aging. J. Cell Commun. Signal. 12, 35–43 (2018). https://doi.org/10.1007/s12079-018-0459-1

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