PMID- 30320382
OWN - NLM
STAT- MEDLINE
DCOM- 20190225
LR  - 20190225
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 42
IP  - 6
DP  - 2018 Dec
TI  - LOXL2, a copper-dependent monoamine oxidase, activates lung fibroblasts through 
      the TGF-beta/Smad pathway.
PG  - 3530-3541
LID - 10.3892/ijmm.2018.3927 [doi]
AB  - A previous study demonstrated that Lysyl oxidase‑like 2 (LOXL2) serves an 
      essential role in matrix remodeling and fibrogenesis, thus indicating its 
      involvement in fibrosis‑associated diseases. Our previous studies revealed a 
      novel association between LOXL2 expression and pulmonary fibrosis in mice. 
      However, the exact role and mechanisms of LOXL2 in interstitial lung disease 
      remain poorly understood. The present study aimed to detect LOXL2 expression in 
      mice with bleomycin (BLM)‑induced pulmonary fibrosis, and explore the effects of 
      silencing LOXL2 on the proliferation, activation and fibrosis process of mouse 
      lung fibroblasts (MLFs). In addition, the present study investigated the 
      association between LOXL2 and the transforming growth factor-beta (TGF‑beta)/Smad 
      signaling pathway to identify the mechanism underlying the role of LOXL2 in 
      fibrosis progression. An animal model of pulmonary fibrosis was established by 
      administering an intratracheal injection of 5 mg/kg BLM to C57BL/6 mice. ELISA 
      and immunohistochemical examination were used to detect the LOXL2 level in the 
      serum, lung homogenate and pulmonary tissues in mice. Pulmonary tissues of mice 
      were extracted to culture primary MLFs, and a LOXL2 small interfering RNA 
      adenovirus vector was established to silence LOXL2 in MLFs. Cell proliferation 
      was detected using the cell counting kit‑8 assay. Reverse 
      transcription‑quantitative polymerase chain reaction and western blotting were 
      used to measure the expression of LOXL2, TGF‑beta1, Smad2/3, 
      phosphorylated (p)Smad2/3, Smad4, and Smad7 and Snail in cells. 
      Interleukin‑6 (IL‑6) and type 1 collagen alpha1 (COL1A1) in the supernatant of cells 
      were analyzed by ELISA. It was demonstrated that LOXL2 expression was 
      significantly increased in serum, lung homogenate and pulmonary tissues of mice 
      with BLM‑induced pulmonary fibrosis compared with control mice. Furthermore, 
      silencing LOXL2 significantly decreased MLF proliferation, and the levels of IL‑6 
      and COL1A1 in the supernatant of cells. Furthermore, silencing LOXL2 inhibited 
      the expression of pSmad2/3, Smad4 and Snail, while it promoted Smad7 expression. 
      The present data provides a comprehensive analysis of the LOXL2 in pulmonary 
      fibrosis and indicates prominent roles for LOXL2 in fibrogenesis via regulation 
      of the TGF‑beta/Smad signaling pathway.
FAU - Wen, Xiaohong
AU  - Wen X
AD  - Department of Rheumatology and Immunology, Beijing Chaoyang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Rheumatology, First Affiliated Hospital of Baotou Medical College, 
      Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia 
      014010, P.R. China.
FAU - Bai, Yu
AU  - Bai Y
AD  - Department of Rheumatology and Immunology, Beijing Chaoyang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
FAU - Li, Mingwei
AU  - Li M
AD  - Department of Rheumatology and Immunology, Fu Xing Hospital, Capital Medical 
      University, Beijing 100038, P.R. China.
FAU - Fu, Qiang
AU  - Fu Q
AD  - Department of Rheumatology and Immunology, Beijing Chaoyang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
FAU - Zheng, Yi
AU  - Zheng Y
AD  - Department of Rheumatology and Immunology, Beijing Chaoyang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181011
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Smad Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 11056-06-7 (Bleomycin)
RN  - 789U1901C5 (Copper)
RN  - EC 1.4.- (Amino Acid Oxidoreductases)
RN  - EC 1.4.3.- (Loxl2 protein, mouse)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
SB  - IM
MH  - Adenoviridae/metabolism
MH  - Amino Acid Oxidoreductases/*metabolism
MH  - Animals
MH  - Bleomycin
MH  - Cell Proliferation
MH  - Copper/*metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Fibroblasts/*metabolism/*pathology
MH  - Gene Silencing
MH  - Genetic Vectors/metabolism
MH  - Lung/diagnostic imaging/*pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Monoamine Oxidase/*metabolism
MH  - Pulmonary Fibrosis/diagnostic imaging/enzymology/pathology
MH  - RNA, Small Interfering/metabolism
MH  - Signal Transduction
MH  - Smad Proteins/*metabolism
MH  - Transforming Growth Factor beta/*metabolism
EDAT- 2018/10/16 06:00
MHDA- 2019/02/26 06:00
CRDT- 2018/10/16 06:00
PHST- 2018/01/02 00:00 [received]
PHST- 2018/10/04 00:00 [accepted]
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2019/02/26 06:00 [medline]
PHST- 2018/10/16 06:00 [entrez]
AID - 10.3892/ijmm.2018.3927 [doi]
PST - ppublish
SO  - Int J Mol Med. 2018 Dec;42(6):3530-3541. doi: 10.3892/ijmm.2018.3927. Epub 2018 
      Oct 11.