PMID- 33217999 OWN - NLM STAT- MEDLINE DCOM- 20210304 LR - 20210304 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 22 DP - 2020 Nov 18 TI - Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging. LID - 10.3390/ijms21228693 [doi] LID - 8693 AB - 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-beta1 (TGF-beta1) mRNA and upregulated the expression of type I collagen by activating the TGF-beta 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. FAU - Choi, Young Eun AU - Choi YE AUID- ORCID: 0000-0003-3815-4833 AD - Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea. FAU - Song, Min Ji AU - Song MJ AUID- ORCID: 0000-0002-5252-4522 AD - Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea. FAU - Hara, Mari AU - Hara M AD - Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan. FAU - Imanaka-Yoshida, Kyoko AU - Imanaka-Yoshida K AUID- ORCID: 0000-0002-8919-7342 AD - Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu 514-8507, Japan. AD - Mie University Research Center for Matrix Biology, Tsu 514-8507, Japan. FAU - Lee, Dong Hun AU - Lee DH AD - Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea. AD - Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea. FAU - Chung, Jin Ho AU - Chung JH AD - Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea. AD - Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, Korea. FAU - Lee, Seung-Taek AU - Lee ST AUID- ORCID: 0000-0001-7300-9784 AD - Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea. LA - eng PT - Journal Article DEP - 20201118 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (RNA, Messenger) RN - 0 (SMAD2 protein, human) RN - 0 (SMAD3 protein, human) RN - 0 (Smad2 Protein) RN - 0 (Smad2 protein, mouse) RN - 0 (Smad3 Protein) RN - 0 (Smad3 protein, mouse) RN - 0 (TGFB1 protein, human) RN - 0 (TNC protein, human) RN - 0 (Tenascin) RN - 0 (Tgfb1 protein, mouse) RN - 0 (Tnc protein, mouse) RN - 0 (Transforming Growth Factor beta1) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, mouse) RN - EC 3.4.24.7 (MMP1 protein, human) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Animals MH - Extracellular Matrix/genetics/*metabolism MH - Female MH - Humans MH - Matrix Metalloproteinase 1/genetics/metabolism MH - Matrix Metalloproteinase 13/genetics/metabolism MH - Mice MH - Mice, Hairless MH - RNA, Messenger/genetics/metabolism MH - *Signal Transduction MH - *Skin Aging MH - Smad2 Protein/genetics/metabolism MH - Smad3 Protein/genetics/metabolism MH - Tenascin/genetics/*metabolism MH - Transforming Growth Factor beta1/genetics/metabolism PMC - PMC7698786 OTO - NOTNLM OT - TGF-beta OT - aging OT - collagen OT - extracellular matrix OT - fibroblast OT - skin OT - tenascin C COIS- The authors declare no conflict of interest. EDAT- 2020/11/22 06:00 MHDA- 2021/03/05 06:00 PMCR- 2020/11/01 CRDT- 2020/11/21 01:01 PHST- 2020/10/27 00:00 [received] PHST- 2020/11/14 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/11/21 01:01 [entrez] PHST- 2020/11/22 06:00 [pubmed] PHST- 2021/03/05 06:00 [medline] PHST- 2020/11/01 00:00 [pmc-release] AID - ijms21228693 [pii] AID - ijms-21-08693 [pii] AID - 10.3390/ijms21228693 [doi] PST - epublish SO - Int J Mol Sci. 2020 Nov 18;21(22):8693. doi: 10.3390/ijms21228693.