PMID- 26302720
OWN - NLM
STAT- MEDLINE
DCOM- 20160525
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 37
IP  - 1
DP  - 2015
TI  - Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar 
      Disc Degeneration.
PG  - 225-32
LID - 10.1159/000430347 [doi]
AB  - BACKGROUND/AIMS: The pathogenesis of Lumbar disc degeneration (LDD) has been 
      extensively studied in the past. In particular, a role of matrix 
      metalloproteinase 3 (MMP3) in the disease initiation and progression has been 
      recently reported. However, an involvement of Insulin-like growth factor 1 
      (IGF-I)-stimulated phosphatidylinositol-3 kinase (PI3k) / Akt signaling 
      pathway-mediated control of MMP3 in LDD has not been acknowledged. METHODS: We 
      examined the serum IGF-1 levels and activation of the receptor for IGF-1 (IGF-1R) 
      in resected discs in patients with LDD, compared to the fractured discs from 
      traumatized, non-LDD subjects as a control. We analyzed the effects of IGF-1 on 
      the activation of IGF-1R, Akt and MMP3 in a human nucleus pulposus SV40 cell line 
      (HNPSV). We transfected HNPSV cells with a constitutive nuclear FoxO1, and 
      analyzed its effect on the activation of IGF-1R, Akt and MMP3. RESULTS: LDD 
      patients had significantly lower levels of serum IGF-1, and LDD discs had 
      significantly lower levels of activated IGF-1R. IGF-1 induced phosphorylation of 
      IGF-1R, and then phosphorylation of its downstream factor Akt in the HNPSV cells, 
      resulting in significantly inhibition of MMP3. Further, FoxO1 nuclear retention 
      completely abolished the inhibitory effects of IGF-1 on MMP3 in HNPSV cells. 
      CONCLUSION: Together, IGF-1/Akt/FoxO1/MMP3 regulatory machinery may control the 
      development of LDD.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Liu, Zuoqing
AU  - Liu Z
AD  - Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 
      China.
FAU - Zhou, Kaihua
AU  - Zhou K
FAU - Fu, Wenqin
AU  - Fu W
FAU - Zhang, Hailong
AU  - Zhang H
LA  - eng
PT  - Journal Article
DEP - 20150820
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Cell Line
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Intervertebral Disc Degeneration/*metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation/physiology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Receptor, IGF Type 1/metabolism
MH  - Signal Transduction/*physiology
EDAT- 2015/08/26 06:00
MHDA- 2016/05/26 06:00
CRDT- 2015/08/26 06:00
PHST- 2015/06/17 00:00 [accepted]
PHST- 2015/08/26 06:00 [entrez]
PHST- 2015/08/26 06:00 [pubmed]
PHST- 2016/05/26 06:00 [medline]
AID - 000430347 [pii]
AID - 10.1159/000430347 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2015;37(1):225-32. doi: 10.1159/000430347. Epub 2015 Aug 
      20.