PMID- 27720345 OWN - NLM STAT- MEDLINE DCOM- 20180307 LR - 20211204 IS - 0929-6646 (Print) IS - 0929-6646 (Linking) VI - 116 IP - 5 DP - 2017 May TI - Transforming growth factor beta 1 increases collagen content, and stimulates procollagen I and tissue inhibitor of metalloproteinase-1 production of dental pulp cells: Role of MEK/ERK and activin receptor-like kinase-5/Smad signaling. PG - 351-358 LID - S0929-6646(16)30200-5 [pii] LID - 10.1016/j.jfma.2016.07.014 [doi] AB - BACKGROUND/PURPOSE: In order to clarify the role of transforming growth factor beta 1 (TGF-beta1) in pulp repair/regeneration responses, we investigated the differential signaling pathways responsible for the effects of TGF-beta1 on collagen turnover, matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-1 (TIMP-1) production in human dental pulp cells. METHODS: Pulp cells were exposed to TGF-beta1 with/without pretreatment and coincubation by 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenyl mercapto)butadiene (U0126; a mitogen-activated protein kinase kinase [MEK]/extracellular signal-regulated kinase [ERK] inhibitor) and 4-(5-benzol[1,3]dioxol-5-yl-4-pyrldin-2-yl-1H- imidazol-2-yl)-benzamide hydrate (SB431542; an activin receptor-like kinase-5/Smad signaling inhibitor). Sircol collagen assay was used to measure cellular collagen content. Culture medium procollagen I, TIMP-1, and MMP-3 levels were determined by enzyme-linked immunosorbent assay. RESULTS: TGF-beta1 increased the collagen content, procollagen I, and TIMP-1 production, but slightly decreased MMP-3 production of pulp cells. SB431542 and U0126 prevented the TGF-beta1-induced increase of collagen content and TIMP-1 production of dental pulp cells. CONCLUSION: These results indicate that TGF-beta1 may be involved in the healing/regeneration processes of dental pulp in response to injury by stimulation of collagen and TIMP-1 production. These events are associated with activin receptor-like kinase-5/Smad2/3 and MEK/ERK signaling. CI - Copyright (c) 2016. Published by Elsevier B.V. FAU - Lin, Po-Shuen AU - Lin PS AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. FAU - Chang, Hsiao-Hua AU - Chang HH AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. FAU - Yeh, Chien-Yang AU - Yeh CY AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. FAU - Chang, Mei-Chi AU - Chang MC AD - Biomedical Science Team, Chang Gung University of Science and Technology, Kwei-Shan, Taoyuan City, Taiwan; Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan. Electronic address: mcchang@mail.cgust.edu.tw. FAU - Chan, Chiu-Po AU - Chan CP AD - Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan. FAU - Kuo, Han-Yueh AU - Kuo HY AD - Department of Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. FAU - Liu, Hsin-Cheng AU - Liu HC AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. FAU - Liao, Wan-Chuen AU - Liao WC AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. FAU - Jeng, Po-Yuan AU - Jeng PY AD - School of Dentistry, University of Cardenal Herrera, CEU, Valencia, Spain. FAU - Yeung, Sin-Yuet AU - Yeung SY AD - Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan. FAU - Jeng, Jiiang-Huei AU - Jeng JH AD - Graduate Institute of Clinical Dentistry & Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan. Electronic address: jhjeng@ntu.edu.tw. LA - eng PT - Journal Article DEP - 20161006 PL - Singapore TA - J Formos Med Assoc JT - Journal of the Formosan Medical Association = Taiwan yi zhi JID - 9214933 RN - 0 (4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide) RN - 0 (Benzamides) RN - 0 (Butadienes) RN - 0 (Collagen Type I) RN - 0 (Dioxoles) RN - 0 (Nitriles) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Smad Proteins) RN - 0 (TIMP1 protein, human) RN - 0 (Tissue Inhibitor of Metalloproteinase-1) RN - 0 (Transforming Growth Factor beta1) RN - 0 (U 0126) RN - 9007-34-5 (Collagen) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) RN - EC 2.7.11.30 (TGFBR1 protein, human) SB - IM MH - Benzamides/pharmacology MH - Butadienes/pharmacology MH - Cells, Cultured MH - Collagen/*physiology MH - Collagen Type I/*metabolism MH - Dental Pulp/cytology MH - Dioxoles/pharmacology MH - Humans MH - MAP Kinase Signaling System/drug effects/physiology MH - Nitriles/pharmacology MH - Protein Serine-Threonine Kinases/drug effects/physiology MH - Receptor, Transforming Growth Factor-beta Type I MH - Receptors, Transforming Growth Factor beta/drug effects/physiology MH - Regeneration/drug effects/*physiology MH - Smad Proteins/drug effects/physiology MH - Tissue Inhibitor of Metalloproteinase-1/*metabolism MH - Transforming Growth Factor beta1/*physiology OTO - NOTNLM OT - activin receptor-like kinase-5 OT - collagen OT - dental pulp cells OT - signal transduction OT - tissue inhibitor of metalloproteinase-1 OT - transforming growth factor beta EDAT- 2016/10/11 06:00 MHDA- 2018/03/08 06:00 CRDT- 2016/10/11 06:00 PHST- 2016/05/15 00:00 [received] PHST- 2016/07/05 00:00 [revised] PHST- 2016/07/07 00:00 [accepted] PHST- 2016/10/11 06:00 [pubmed] PHST- 2018/03/08 06:00 [medline] PHST- 2016/10/11 06:00 [entrez] AID - S0929-6646(16)30200-5 [pii] AID - 10.1016/j.jfma.2016.07.014 [doi] PST - ppublish SO - J Formos Med Assoc. 2017 May;116(5):351-358. doi: 10.1016/j.jfma.2016.07.014. Epub 2016 Oct 6.