PMID- 37340717
OWN - NLM
STAT- MEDLINE
DCOM- 20230622
LR  - 20230701
IS  - 1473-2300 (Electronic)
IS  - 0300-0605 (Print)
IS  - 0300-0605 (Linking)
VI  - 51
IP  - 6
DP  - 2023 Jun
TI  - Activation of the mTOR pathway promotes neurite growth through upregulation of 
      CD44 expression.
PG  - 3000605231178510
LID - 10.1177/03000605231178510 [doi]
LID - 03000605231178510
AB  - OBJECTIVE: To explore the intrinsic mechanism of the mammalian target of 
      rapamycin (mTOR) pathway activation and promotion of neuronal axon growth. 
      METHODS: Human neuroblastoma cells, SH-SY5Y, were induced with all-trans retinoic 
      acid (ATRA; 10 muM for three days) which differentiated the cell line into a 
      neuronal-like state. Immunohistochemical staining was used to detect the 
      differentiation status of the neuronal-like cells. Phosphatase and tensin homolog 
      (PTEN) RNA interference (RNAi) experiments were performed on the differentiated 
      cells; reverse transcription-polymerase chain reaction (RT-PCR) detected 
      transcriptional levels of PTEN following 24 h of interference. After 36 h, 
      western blot assay was used to detect expression levels of ribosomal protein S6 
      kinase (pS6k) and mTOR. To downregulate the expression of PTEN and cluster of 
      differentiation 44 (CD44), a cell-surface glycoprotein, simultaneously, PTEN 
      siRNA and CD44 siRNA sequences were mixed in equal proportions in co-interference 
      experiments. RT-PCR detected the transcription level of CD44, and the 
      relationship between the CD44 and axonal growth was observed after 48 h of 
      interference. RESULTS: Microtubule-associated protein 2 (MAP2) expression was 
      enhanced after three days of induction in SH-SY5Y cells. RT-PCR showed the 
      transcription level of PTEN was significantly downregulated after 24 h of PTEN 
      knockdown. mTOR and pS6k protein expression levels were significantly upregulated 
      after 36 h of interference. CD44 transcription levels were upregulated after PTEN 
      gene interference. The neurite length of the cells in the experimental 
      interference group was significantly longer than that in the control group, and 
      the expression level of CD44 was positively correlated with neurite growth. The 
      neurite length of the PTEN-only interference group was significantly greater than 
      that of the co-interference and ATRA groups. CONCLUSION: Activation of the mTOR 
      pathway promoted neurite growth through upregulation of CD44 expression, thus 
      promoting neuronal regeneration.
FAU - Zhang, Jiwei
AU  - Zhang J
AUID- ORCID: 0000-0002-1658-7390
AD  - Department of Pathology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou, Jiangsu, 215123, China. RINGGOLD: 606537
FAU - Gan, Wenjuan
AU  - Gan W
AD  - Department of Pathology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou, Jiangsu, 215123, China. RINGGOLD: 606537
FAU - Peng, Ru
AU  - Peng R
AD  - Department of Histology and Embryology College of Basic Medical Sciences, Jilin 
      University, No. 828, Xinmin Road Changchun 130061, China. RINGGOLD: 12510
FAU - Lu, Lei
AU  - Lu L
AD  - Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow 
      University, Suzhou 215021, China. RINGGOLD: 12582
FAU - Lu, Weiqing
AU  - Lu W
AD  - Department of Pathology, Dushu Lake Hospital Affiliated to Soochow University, 
      Suzhou, Jiangsu, 215123, China. RINGGOLD: 606537
FAU - Liu, Jiamei
AU  - Liu J
AD  - Department of Histology and Embryology College of Basic Medical Sciences, Jilin 
      University, No. 828, Xinmin Road Changchun 130061, China. RINGGOLD: 12510
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Int Med Res
JT  - The Journal of international medical research
JID - 0346411
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - 0 (CD44 protein, human)
RN  - 0 (Hyaluronan Receptors)
SB  - IM
MH  - Humans
MH  - Up-Regulation
MH  - *Neurites/metabolism
MH  - Sirolimus
MH  - *Neuroblastoma/genetics
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - PTEN Phosphohydrolase/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Hyaluronan Receptors/genetics
PMC - PMC10288410
OTO - NOTNLM
OT  - Axonal growth
OT  - CD44
OT  - Nerve regeneration
OT  - mTOR pathway
EDAT- 2023/06/21 06:42
MHDA- 2023/06/22 06:42
PMCR- 2023/06/20
CRDT- 2023/06/21 02:13
PHST- 2023/06/22 06:42 [medline]
PHST- 2023/06/21 06:42 [pubmed]
PHST- 2023/06/21 02:13 [entrez]
PHST- 2023/06/20 00:00 [pmc-release]
AID - 10.1177_03000605231178510 [pii]
AID - 10.1177/03000605231178510 [doi]
PST - ppublish
SO  - J Int Med Res. 2023 Jun;51(6):3000605231178510. doi: 10.1177/03000605231178510.