Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging.

Young Eun Choi,Seung-Taek Lee,Jin Ho Chung,Kyoko Imanaka-Yoshida,Mari Hara,Dong Hun Lee,Min Ji Song

doi:10.3390/ijms21228693

Young Eun Choi, Seung-Taek Lee + Show 5 more

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https://doi.org/10.3390/ijms21228693

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Abstract

Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.

Highlights

Tenascin C (TNC) is a multimodular extracellular matrix (ECM) protein with multiple molecular forms that are generated by alternative splicing and post-translational modifications [1]
Tnc mRNA levels showed a significant decrease in the skin tissues of aged mice compared with young mice (Figure 1A)
IHC staining of young skin tissues revealed that TNC signals were present in the dermis as well as the epidermis, in the basal layer (Figure 1B)

Summary

Introduction

Tenascin C (TNC) is a multimodular extracellular matrix (ECM) protein with multiple molecular forms that are generated by alternative splicing and post-translational modifications [1]. TNC contains an assembly domain essential for the formation of hexamers, epidermal growth factor (EGF)-like repeats, fibronectin type III-like repeats, and a C-terminal fibrinogen-like globular domain. TNC is not an obligatory structural element of the ECM, it binds to structural proteins and cell surface receptors such as the EGF receptor and integrins in the ECM [7,8,9,10]. Binding of TNC to these receptors activates their downstream pathways and affects cell proliferation, adhesion, and migration, depending on cell types and environments [11,12,13,14,15]

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