PMID- 31198002 OWN - NLM STAT- MEDLINE DCOM- 20190830 LR - 20220410 IS - 1002-1892 (Print) IS - 1002-1892 (Linking) VI - 33 IP - 6 DP - 2019 Jun 15 TI - [Mechanism of p38 mitogen activated protein kinase signaling pathway on promoting the hypertrophy of human lumbar ligamentum flavum via transforming growth factor beta (1)/connective tissue growth factor]. PG - 730-735 LID - 10.7507/1002-1892.201811140 [doi] AB - OBJECTIVE: To investigate the mechanism of p38 mitogen activated protein kinase (MAPK) signaling pathway in regulating the hyperplasia and hypertrophy of human lumbar ligamentum flavum via transforming growth factor beta (1) (TGF-beta (1))/connective tissue growth factor (CTGF). METHODS: The lumbar ligamentum flavum tissue taken from patient with lumbar intervertebral disc herniation was isolated by collagenase-predigested explant cultures. The ligamentum flavum cells were treated with the extracellular regulated protein kinase pathway blocker PD98059, c-Jun N-terminal kinase pathway blocker SP600125, and p38 pathway blocker SB203580, and then the mRNA expressions of CTGF, collagen type Ⅰ, and collagen type Ⅲ were detected by real-time fluorescence quantitative PCR (qRT-PCR). The ligamentum flavum cells were divided into 4 groups, and transfected with small interfering RNA (siRNA), p38 siRNA, siRNA+3 ng/mL TGF-beta (1), and p38 siRNA+3 ng/mL TGF-beta (1) in groups A, B, C, and D, respectively. After 24 hours of transfection, immunofluorescence staining was performed to observe the expressions of p38 and phosphorylation p38 (p-p38); the relative mRNA expressions of CTGF, collagen type Ⅰ, and collagen type Ⅲ in each group were detected by qRT-PCR; the protein expression of CTGF in each group was detected by Western blot. RESULTS: p38 pathway blocker SB203580 could significantly reduce the relative mRNA expressions of CTGF, collagen type Ⅰ, and collagen type Ⅲ ( P<0.05). After 24 hours of transfection, immunofluorescence staining showed positive staining with p38 and p-p38 expressions in groups A, C, and D and negative staining in group B. Compared with group A, the relative mRNA expressions of CTGF, collagen type Ⅰ, and collagen type Ⅲ and relative protein expression of CTGF in group B decreased significantly ( P<0.05), while those in groups C and D increased significantly ( P<0.05); and those indicators significantly increased in group C than in group D ( P<0.05). CONCLUSION: TGF-beta (1)/CTGF based on the p38 MAPK signaling pathway play an important role in the occurance and development of hypertrophy of human lumbar ligamentum flavum. FAU - Lu, Changhuai AU - Lu C AD - Department of Spine Disease Area of Orthopedics and Traumatology, No.1 Traditional Chinese Medicine Hospital of Changde, Changde Hospital Affiliated to Hunan University of Traditional Chinese Medicine, Changde Hunan, 415000, P.R.China. FAU - Liu, Zhijun AU - Liu Z AD - Department of Spine Disease Area of Orthopedics and Traumatology, No.1 Traditional Chinese Medicine Hospital of Changde, Changde Hospital Affiliated to Hunan University of Traditional Chinese Medicine, Changde Hunan, 415000, P.R.China. FAU - Zhang, Hongbo AU - Zhang H AD - Department of Spine Disease Area of Orthopedics and Traumatology, No.1 Traditional Chinese Medicine Hospital of Changde, Changde Hospital Affiliated to Hunan University of Traditional Chinese Medicine, Changde Hunan, 415000, P.R.China. FAU - Duan, Yang AU - Duan Y AD - Department of Spinal Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou Guangdong, 510282, P.R.China.duanyang2011@163.com. FAU - Cao, Yanlin AU - Cao Y AD - Department of Spinal Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou Guangdong, 510282, P.R.China. LA - chi PT - Journal Article PL - China TA - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi JT - Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery JID - 9425194 RN - 0 (CCN2 protein, human) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cells, Cultured MH - *Connective Tissue Growth Factor/physiology MH - Humans MH - Hypertrophy MH - *Ligamentum Flavum/metabolism MH - *Signal Transduction MH - Transforming Growth Factor beta MH - Transforming Growth Factor beta1/physiology MH - *p38 Mitogen-Activated Protein Kinases/physiology PMC - PMC8355761 OTO - NOTNLM OT - Mitogen activated protein kinase OT - connective tissue growth factor OT - ligamentum flavum OT - transforming growth factor beta1 EDAT- 2019/06/15 06:00 MHDA- 2019/08/31 06:00 PMCR- 2019/06/01 CRDT- 2019/06/15 06:00 PHST- 2019/06/15 06:00 [entrez] PHST- 2019/06/15 06:00 [pubmed] PHST- 2019/08/31 06:00 [medline] PHST- 2019/06/01 00:00 [pmc-release] AID - zgxfcjwkzz-33-6-730 [pii] AID - 10.7507/1002-1892.201811140 [doi] PST - ppublish SO - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2019 Jun 15;33(6):730-735. doi: 10.7507/1002-1892.201811140.