PMID- 36382649
OWN - NLM
STAT- MEDLINE
DCOM- 20221118
LR  - 20221220
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 51
IP  - 1
DP  - 2023 Jan
TI  - Laminin alpha1 as a target for the treatment of epidural fibrosis by regulating 
      fibrotic mechanisms.
LID - 2 [pii]
LID - 10.3892/ijmm.2022.5205 [doi]
AB  - Excessive proliferation and migration of fibroblasts in the lumbar laminectomy 
      area can lead to epidural fibrosis, eventually resulting in failed back surgery 
      syndrome. It has been reported that laminin alpha1, a significant biofunctional 
      glycoprotein in the extracellular matrix, is involved in several fibrosis‑related 
      diseases, such as pulmonary, liver and keloid fibrosis. However, the underlying 
      mechanism of laminin alpha1 in epidural fibrosis remains unknown. The present study 
      aimed to explore the effect and mechanism of laminin alpha1 in fibroblast 
      proliferation, apoptosis and migration, and epidural fibrosis. Following the 
      establishment of a laminectomy model, hematoxylin and eosin, Masson's trichrome 
      and immunohistochemical staining were performed to determine the degree of 
      epidural fibrosis, the number of fibroblasts, collagen content and the epidural 
      expression levels of laminin alpha1, respectively. Furthermore, a stable small 
      interfering RNA system was used to knock down the expression of laminin alpha1 in 
      fibroblasts. The transfection efficiency was confirmed by reverse 
      transcription‑quantitative PCR and immunofluorescence staining. Western blot 
      analysis, scratch wound assay, EdU incorporation assay, flow cytometric analysis 
      and Cell Counting Kit 8 assay were performed to assess the proliferation, 
      apoptosis, migration and viability of fibroblasts, as well as the expression 
      levels of the AKT/mechanistic target of rapamycin (mTOR) signaling‑related 
      proteins. In vivo experiments revealed that laminin alpha1 was positively and 
      time‑dependently associated with epidural fibrosis. In addition, laminin alpha1 
      knockdown attenuated cell proliferation, viability and migration, and promoted 
      apoptosis. Furthermore, the results revealed that the activation of the AKT/mTOR 
      signaling pathway was involved in the aforementioned processes. Overall, the 
      current study illustrated the positive association between laminin alpha1 and 
      epidural fibrosis, and also verified the effect of laminin alpha1 on fibroblast 
      proliferation, apoptosis and migration. Furthermore, the results suggested that 
      the AKT/mTOR signaling pathway may serve a significant role in regulating the 
      behavior of laminin alpha1‑induced fibroblasts.
FAU - Liu, Pengran
AU  - Liu P
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Zhang, Dan
AU  - Zhang D
AD  - Department of Pharmacy, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Huang, Guixiong
AU  - Huang G
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Xue, Mingdi
AU  - Xue M
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Fang, Ying
AU  - Fang Y
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Lu, Lin
AU  - Lu L
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Zhang, Jiayao
AU  - Zhang J
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Xie, Mao
AU  - Xie M
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
FAU - Ye, Zhewei
AU  - Ye Z
AD  - Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20221116
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 151186-83-3 (laminin A)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Humans
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - Fibrosis
MH  - *Epidural Space/pathology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Fibroblasts/metabolism
MH  - Cell Proliferation
MH  - Sirolimus/pharmacology
PMC - PMC9728507
OTO - NOTNLM
OT  - AKT/mTOR signaling pathway
OT  - epidural fibrosis
OT  - fibroblasts
OT  - laminectomy
OT  - laminin alpha1
COIS- The authors declared that they have no competing interests.
EDAT- 2022/11/17 06:00
MHDA- 2022/11/19 06:00
PMCR- 2022/11/16
CRDT- 2022/11/16 05:53
PHST- 2022/07/13 00:00 [received]
PHST- 2022/10/25 00:00 [accepted]
PHST- 2022/11/16 05:53 [entrez]
PHST- 2022/11/17 06:00 [pubmed]
PHST- 2022/11/19 06:00 [medline]
PHST- 2022/11/16 00:00 [pmc-release]
AID - 2 [pii]
AID - ijmm-51-1-05205 [pii]
AID - 10.3892/ijmm.2022.5205 [doi]
PST - ppublish
SO  - Int J Mol Med. 2023 Jan;51(1):2. doi: 10.3892/ijmm.2022.5205. Epub 2022 Nov 16.