PMID- 37385615
OWN - NLM
STAT- MEDLINE
DCOM- 20230705
LR  - 20240321
IS  - 1672-7347 (Print)
IS  - 1672-7347 (Linking)
VI  - 48
IP  - 4
DP  - 2023 Apr 28
TI  - MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells.
PG  - 526-537
LID - 1672-7347(2023)04-0526-12 [pii]
LID - 10.11817/j.issn.1672-7347.2023.220326 [doi]
AB  - OBJECTIVES: Nerve growth factor (NGF) induces neuron transdifferentiation of 
      adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the 
      secretion of epinephrine (EPI), which may be involved in the pathogenesis of 
      bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator 
      of neurogenesis in the nervous system, has been proved to be elevated in AMCCs 
      with neuron transdifferentiation in vivo. This study aims to explore the role of 
      MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. 
      METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with 
      siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or 
      dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological 
      changes were observed using light and electron microscope. 
      Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine 
      synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western 
      blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal 
      markers), extracellular regulated protein kinases (ERK), phosphorylated 
      extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was 
      applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular 
      supernatant were measured using ELISA. RESULTS: Cells with both tyrosine 
      hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. 
      Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with 
      increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, 
      impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT 
      level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference 
      reversed the effect of NGF, causing increases in the levels of PNMT and EPI, 
      conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 
      overexpression significantly increased the number of cell processes and 
      peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). 
      Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs 
      in the NGF+PD98059 group were decreased (all P<0.05). After treatment with 
      PD98059 and dexamethasone, the effect of NGF on promoting the 
      transdifferentiation of AMCCs was inhibited, and the number of cell processes and 
      EPI levels were decreased (both P<0.05). In addition, the activity of the 
      pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSIONS: MASH1 is the 
      key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron 
      transdifferentiation is probably mediated via pERK/MASH1 signaling.
FAU - Peng, Emin
AU  - Peng E
AD  - Outpatient Clinic of Xiangya Hospital International Medical Center, Central South 
      University, Changsha 410008. 51318029@qq.com.
FAU - Hu, Chengping
AU  - Hu C
AD  - Department of Respiratory Medicine, National Clinical Key Specialty of 
      Respiratory Disease, Branch of National Clinical Research Center for Respiratory 
      Disease, Xiangya Hospital, Central South University, Changsha 410008.
AD  - Center of Respiratory Medicine, Xiangya Hospital, Central South University, 
      Changsha 410008.
AD  - Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha 
      410008, China.
FAU - Feng, Juntao
AU  - Feng J
AD  - Department of Respiratory Medicine, National Clinical Key Specialty of 
      Respiratory Disease, Branch of National Clinical Research Center for Respiratory 
      Disease, Xiangya Hospital, Central South University, Changsha 410008.
AD  - Center of Respiratory Medicine, Xiangya Hospital, Central South University, 
      Changsha 410008.
AD  - Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha 
      410008, China.
FAU - He, Ruoxi
AU  - He R
AD  - Department of Respiratory Medicine, National Clinical Key Specialty of 
      Respiratory Disease, Branch of National Clinical Research Center for Respiratory 
      Disease, Xiangya Hospital, Central South University, Changsha 410008. 
      heruoxi@csu.edu.cn.
AD  - Center of Respiratory Medicine, Xiangya Hospital, Central South University, 
      Changsha 410008. heruoxi@csu.edu.cn.
AD  - Clinical Research Center for Respiratory Diseases in Hunan Province, Changsha 
      410008, China. heruoxi@csu.edu.cn.
LA  - eng
LA  - chi
GR  - 81400022/the National Natural Science Foundation/
GR  - 2020JJ5897 and 2020JJ4904/the Natural Science Foundation of Hunan Province/
PT  - Journal Article
TT  - MASH1介导肾上腺髓质嗜铬细胞发生神经元转分化.
PL  - China
TA  - Zhong Nan Da Xue Xue Bao Yi Xue Ban
JT  - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. 
      Medical sciences
JID - 101230586
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - YKH834O4BH (Epinephrine)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - 0 (Peripherins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - 0 (Ascl1 protein, rat)
SB  - IM
MH  - Animals
MH  - Rats
MH  - *Adrenal Medulla
MH  - Cell Transdifferentiation
MH  - *Chromaffin Cells
MH  - Dexamethasone
MH  - Epinephrine/pharmacology
MH  - Mammals
MH  - Nerve Growth Factor
MH  - Neurons
MH  - Peripherins
MH  - Protein Kinases
MH  - Tyrosine 3-Monooxygenase
PMC - PMC10930259
OAB - OBJECTIVE: Nerve growth factor (NGF) induces neuron transdifferentiation of 
      adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the 
      secretion of epinephrine (EPI), which may be involved in the pathogenesis of 
      bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator 
      of neurogenesis in the nervous system, has been proved to be elevated in AMCCs 
      with neuron transdifferentiation in vivo. This study aims to explore the role of 
      MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. 
      METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with 
      siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or 
      dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological 
      changes were observed using light and electron microscope. 
      Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine 
      synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western 
      blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal 
      markers), extracellular regulated protein kinases (ERK), phosphorylated 
      extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was 
      applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular 
      supernatant were measured using ELISA. RESULTS: Cells with both tyrosine 
      hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. 
      Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with 
      increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, 
      impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT 
      level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference 
      reversed the effect of NGF, causing increases in the levels of PNMT and EPI, 
      conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 
      overexpression significantly increased the number of cell processes and 
      peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). 
      Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs 
      in the NGF+PD98059 group were decreased (all P<0.05). After treatment with 
      PD98059 and dexamethasone, the effect of NGF on promoting the 
      transdifferentiation of AMCCs was inhibited, and the number of cell processes and 
      EPI levels were decreased (both P<0.05). In addition, the activity of the 
      pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSION: MASH1 is the 
      key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron 
      transdifferentiation is probably mediated via pERK/MASH1 signaling.
OABL- eng
OTO - NOTNLM
OT  - MASH1
OT  - chromaffin cells
OT  - dexamethasone
OT  - nerve growth factor
OT  - neuron
OT  - transdifferentiation
COIS- 作者声称无任何利益冲突。
EDAT- 2023/06/30 01:06
MHDA- 2023/07/03 06:42
PMCR- 2023/04/28
CRDT- 2023/06/29 20:03
PHST- 2023/07/03 06:42 [medline]
PHST- 2023/06/30 01:06 [pubmed]
PHST- 2023/06/29 20:03 [entrez]
PHST- 2023/04/28 00:00 [pmc-release]
AID - 1672-7347(2023)04-0526-12 [pii]
AID - 10.11817/j.issn.1672-7347.2023.220326 [doi]
PST - ppublish
SO  - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Apr 28;48(4):526-537. doi: 
      10.11817/j.issn.1672-7347.2023.220326.