Parasympathetic effect induces cell cycle activation in upper limbs of paraplegic patients with spinal cord injury

Ahreum Baek; Ji Cheol Shin; Min Young Lee; Sung Hoon Kim; Jiyong Kim; Sung Rae Cho

doi:10.3390/ijms20235982

Parasympathetic effect induces cell cycle activation in upper limbs of paraplegic patients with spinal cord injury

Ahreum Baek, Ji Cheol Shin, Min Young Lee, Sung Hoon Kim, Jiyong Kim, Sung Rae Cho

Department of Rehabilitation Medicine

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

The present study aimed to investigate gene expression changes related to cell cycle activation in patients with spinal cord injury (SCI) and to further evaluate the difference between the upper and lower limbs of SCI patients. Fibroblasts were obtained from the upper and lower limbs of SCI patients and healthy subjects. To investigate gene expression profiling in the fibroblasts from SCI patients compared to the healthy subjects, RNA-Seq transcriptome analysis was performed. To validate the parasympathetic effects on cell cycle activation, fibroblasts from upper or lower limbs of SCI patients were treated with the anticholinergic agents tiotropium or acetylcholine, and quantitative RT-PCR and Western blot were conducted. Cell proliferation was significantly increased in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. The pathway and genes involved in cell cycle were identified by RNA-Seq transcriptome analysis. Expression of cell-cycle-related genes CCNB1, CCNB2, PLK1, BUB1, and CDC20 were significantly higher in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. When the fibroblasts were treated with tiotropium the upper limbs and acetylcholine in the lower limbs, the expression of cell-cycle-related genes and cell proliferation were significantly modulated. This study provided the insight that cell proliferation and cell cycle activation were observed to be significantly increased in the upper limbs of SCI patients via the parasympathetic effect.

Original language	English
Article number	5982
Journal	International journal of molecular sciences
Volume	20
Issue number	23
DOIs	https://doi.org/10.3390/ijms20235982
Publication status	Published - 2019 Dec 1

Bibliographical note

Funding Information:
Funding: This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF-2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the “Dongwha” Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042).

Funding Information:
This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the ?Dongwha? Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042). We thank the patients who participated in this study and provided their tissues for medical research.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

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title = "Parasympathetic effect induces cell cycle activation in upper limbs of paraplegic patients with spinal cord injury",

abstract = "The present study aimed to investigate gene expression changes related to cell cycle activation in patients with spinal cord injury (SCI) and to further evaluate the difference between the upper and lower limbs of SCI patients. Fibroblasts were obtained from the upper and lower limbs of SCI patients and healthy subjects. To investigate gene expression profiling in the fibroblasts from SCI patients compared to the healthy subjects, RNA-Seq transcriptome analysis was performed. To validate the parasympathetic effects on cell cycle activation, fibroblasts from upper or lower limbs of SCI patients were treated with the anticholinergic agents tiotropium or acetylcholine, and quantitative RT-PCR and Western blot were conducted. Cell proliferation was significantly increased in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. The pathway and genes involved in cell cycle were identified by RNA-Seq transcriptome analysis. Expression of cell-cycle-related genes CCNB1, CCNB2, PLK1, BUB1, and CDC20 were significantly higher in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. When the fibroblasts were treated with tiotropium the upper limbs and acetylcholine in the lower limbs, the expression of cell-cycle-related genes and cell proliferation were significantly modulated. This study provided the insight that cell proliferation and cell cycle activation were observed to be significantly increased in the upper limbs of SCI patients via the parasympathetic effect.",

author = "Ahreum Baek and Shin, {Ji Cheol} and Lee, {Min Young} and Kim, {Sung Hoon} and Jiyong Kim and Cho, {Sung Rae}",

note = "Funding Information: Funding: This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF-2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the “Dongwha” Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042). Funding Information: This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the ?Dongwha? Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042). We thank the patients who participated in this study and provided their tissues for medical research. Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Baek, Ahreum

AU - Shin, Ji Cheol

AU - Lee, Min Young

AU - Kim, Sung Hoon

AU - Kim, Jiyong

AU - Cho, Sung Rae

N1 - Funding Information: Funding: This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF-2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the “Dongwha” Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042). Funding Information: This research was funded by the National Research Foundation (NRF-2017R1C1B1005407, NRF2018R1A6A3A01013415, NRF-2018R1D1A1B07048239, NRF-2018M3A9G1082609, and NRF-2019R1I1A1A01041292); the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1012); and the ?Dongwha? Faculty Research Assistance Program of Yonsei University College of Medicine (6-2017-0042). We thank the patients who participated in this study and provided their tissues for medical research. Publisher Copyright: © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - The present study aimed to investigate gene expression changes related to cell cycle activation in patients with spinal cord injury (SCI) and to further evaluate the difference between the upper and lower limbs of SCI patients. Fibroblasts were obtained from the upper and lower limbs of SCI patients and healthy subjects. To investigate gene expression profiling in the fibroblasts from SCI patients compared to the healthy subjects, RNA-Seq transcriptome analysis was performed. To validate the parasympathetic effects on cell cycle activation, fibroblasts from upper or lower limbs of SCI patients were treated with the anticholinergic agents tiotropium or acetylcholine, and quantitative RT-PCR and Western blot were conducted. Cell proliferation was significantly increased in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. The pathway and genes involved in cell cycle were identified by RNA-Seq transcriptome analysis. Expression of cell-cycle-related genes CCNB1, CCNB2, PLK1, BUB1, and CDC20 were significantly higher in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. When the fibroblasts were treated with tiotropium the upper limbs and acetylcholine in the lower limbs, the expression of cell-cycle-related genes and cell proliferation were significantly modulated. This study provided the insight that cell proliferation and cell cycle activation were observed to be significantly increased in the upper limbs of SCI patients via the parasympathetic effect.

AB - The present study aimed to investigate gene expression changes related to cell cycle activation in patients with spinal cord injury (SCI) and to further evaluate the difference between the upper and lower limbs of SCI patients. Fibroblasts were obtained from the upper and lower limbs of SCI patients and healthy subjects. To investigate gene expression profiling in the fibroblasts from SCI patients compared to the healthy subjects, RNA-Seq transcriptome analysis was performed. To validate the parasympathetic effects on cell cycle activation, fibroblasts from upper or lower limbs of SCI patients were treated with the anticholinergic agents tiotropium or acetylcholine, and quantitative RT-PCR and Western blot were conducted. Cell proliferation was significantly increased in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. The pathway and genes involved in cell cycle were identified by RNA-Seq transcriptome analysis. Expression of cell-cycle-related genes CCNB1, CCNB2, PLK1, BUB1, and CDC20 were significantly higher in the upper limbs of SCI patients compared with the lower limbs of SCI patients and healthy subjects. When the fibroblasts were treated with tiotropium the upper limbs and acetylcholine in the lower limbs, the expression of cell-cycle-related genes and cell proliferation were significantly modulated. This study provided the insight that cell proliferation and cell cycle activation were observed to be significantly increased in the upper limbs of SCI patients via the parasympathetic effect.

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Parasympathetic effect induces cell cycle activation in upper limbs of paraplegic patients with spinal cord injury

Abstract

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