PMID- 28887384
OWN - NLM
STAT- MEDLINE
DCOM- 20171012
LR  - 20171217
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 474
IP  - 20
DP  - 2017 Oct 5
TI  - Constitutive activation of p46JNK2 is indispensable for C/EBPdelta induction in the 
      initial stage of adipogenic differentiation.
PG  - 3421-3437
LID - 10.1042/BCJ20170332 [doi]
AB  - Adipogenic differentiation plays a vital role in energy homeostasis and endocrine 
      system. Several transcription factors, including peroxisome 
      proliferator-activated receptor gamma 2 and CCAAT-enhancer-binding protein 
      (C/EBP) alpha, beta, and delta, are important for the process, whereas the stage-specific 
      intracellular signal transduction regulating the onset of adipogenesis remains 
      enigmatic. Here, we explored the functional role of c-jun N-terminal kinases 
      (JNKs) in adipogenic differentiation using in vitro differentiation models of 
      3T3-L1 cells and primary adipo-progenitor cells. JNK inactivation with either a 
      pharmacological inhibitor or JNK2-specific siRNA suppressed adipogenic 
      differentiation, characterized by decreased lipid droplet appearance and the 
      down-regulation of Adiponectin, fatty acid protein 4 (Fabp4), Pparg2, and C/ebpa 
      expressions. Conversely, increased adipogenesis was observed by the inducible 
      overexpression of p46JNK2 (JNK2-1), whereas it was not observed by that of 
      p54JNK2 (JNK2-2), indicating a distinct role of p46JNK2. The essential role of 
      JNK appears restricted to the early stage of adipogenic differentiation, as JNK 
      inhibition in the later stages did not influence adipogenesis. Indeed, JNK 
      phosphorylation was significantly induced at the onset of adipogenic 
      differentiation. As for the transcription factors involved in early adipogenesis, 
      JNK inactivation significantly inhibited the induction of C/ebpd, but not C/ebpb, 
      during the initial stage of adipogenic differentiation. JNK activation increased 
      C/ebpd mRNA and protein expression through the induction and phosphorylation of 
      activating transcription factor 2 (ATF2) that binds to a responsive element 
      within the C/ebpd gene promoter region. Taken together, these data indicate that 
      constitutive JNK activity is specifically required for the initial stage 
      differentiation events of adipocytes.
CI  - (c) 2017 The Author(s). Published by Portland Press Limited on behalf of the 
      Biochemical Society.
FAU - Kusuyama, Joji
AU  - Kusuyama J
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 
      Kagoshima 890-8544, Japan.
FAU - Ohnishi, Tomokazu
AU  - Ohnishi T
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 
      Kagoshima 890-8544, Japan.
FAU - Bandow, Kenjiro
AU  - Bandow K
AD  - Department of Oral Biology and Tissue Engineering, Meikai University School of 
      Dentistry, 1-1 Keyakidai, Sakato 350-0283, Japan.
FAU - Amir, Muhammad Subhan
AU  - Amir MS
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 
      Kagoshima 890-8544, Japan.
AD  - Department of Oral and Maxillofacial Surgery, Field of Oral and Maxillofacial 
      Rehabilitation, Kagoshima University Graduate School of Medical and Dental 
      Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
AD  - Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Airlangga 
      University, Campus A UNAIR, JL. Mayjen Professor Doktor Moestopo No. 47, Pacar 
      Kembang, Tambaksari, Kota SBY, Surabaya, Jawa Timur 60132, Indonesia.
FAU - Shima, Kaori
AU  - Shima K
AD  - Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate 
      School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, 
      Japan.
FAU - Semba, Ichiro
AU  - Semba I
AD  - Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate 
      School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, 
      Japan.
FAU - Matsuguchi, Tetsuya
AU  - Matsuguchi T
AD  - Department of Oral Biochemistry, Field of Developmental Medicine, Kagoshima 
      University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, 
      Kagoshima 890-8544, Japan tmatsugu@dent.kagoshima-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171005
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Anthracenes)
RN  - 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - EC 2.7.1.24 (Mitogen-Activated Protein Kinase 9)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/drug effects/metabolism
MH  - Adipogenesis/drug effects/*physiology
MH  - Animals
MH  - Anthracenes/pharmacology
MH  - CCAAT-Enhancer-Binding Protein-delta/*biosynthesis
MH  - Cell Differentiation/drug effects/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase 9/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - ATF2
OT  - C/EBPdelta
OT  - Janus kinase
OT  - adipocytes
OT  - adipogenesis
EDAT- 2017/09/10 06:00
MHDA- 2017/10/13 06:00
CRDT- 2017/09/10 06:00
PHST- 2017/05/04 00:00 [received]
PHST- 2017/08/14 00:00 [revised]
PHST- 2017/08/24 00:00 [accepted]
PHST- 2017/09/10 06:00 [pubmed]
PHST- 2017/10/13 06:00 [medline]
PHST- 2017/09/10 06:00 [entrez]
AID - BCJ20170332 [pii]
AID - 10.1042/BCJ20170332 [doi]
PST - epublish
SO  - Biochem J. 2017 Oct 5;474(20):3421-3437. doi: 10.1042/BCJ20170332.