PMID- 36004621
OWN - NLM
STAT- MEDLINE
DCOM- 20221003
LR  - 20221003
IS  - 1897-5631 (Electronic)
IS  - 0239-8508 (Linking)
VI  - 60
IP  - 3
DP  - 2022
TI  - HIPK2 attenuates bleomycin-induced pulmonary fibrosis by suppressing the 
      Wnt/beta-catenin signaling pathway.
PG  - 247-259
LID - 10.5603/FHC.a2022.0022 [doi]
AB  - INTRODUCTION: The present study aimed to investigate the effect of homeodomain 
      interacting protein kinase 2 (HIPK2) on pulmonary fibrosis and the probable 
      mechanisms. MATERIAL AND METHODS: We constructed a mouse model of 
      bleomycin-induced pulmonary fibrosis and up-regulated the expression of HIPK2 in 
      the lung by in vivo transfection. Lung tissues were collected for the detection 
      of mesenchymal markers (alpha-SMA, collagen I, collagen III) and the expression of 
      beta-catenin as assessed by RT-PCR, western blot, and immunohistochemistry. Mouse 
      lung fibroblasts (MLFs) with upregulation or downregulation of HIPK2 were 
      successfully constructed and XAV939 was used to downregulate beta-catenin 
      expression. Then, we evaluated the activation of MLFs and the Wnt/beta-catenin 
      pathway under various conditions. RESULTS: The results showed that in the 
      bleomycin-induced mouse model group, the lung alveolar structure was severely 
      damaged, the amount of collagen fibers was increased in alveolar speta, and the 
      expression of HIPK2 in the fibrotic area was found to be reduced. After 
      upregulating HIPK2 in the lungs of the mouse fibrosis model we found that 
      pulmonary fibrosis was attenuated and the expression of beta-catenin and mesenchymal 
      markers was reduced. The upregulation of HIPK2 inhibited the proliferation and 
      migration of MLFs induced by TGF-beta1, promoted apoptosis of MLFs, and reduced the 
      expression of mesenchymal markers and beta-catenin. Meanwhile, downregulation of 
      HIPK2 promoted the proliferation and migration of MLFs, inhibited apoptosis, and 
      promoted mesenchymal markers and beta-catenin expression. XAV939 treatment of MLFs 
      silencing HIPK2 inhibited their proliferation and activation via silencing HIPK2, 
      promoted apoptosis, and reduced interstitial markers and beta-catenin expression. 
      CONCLUSIONS: HIPK2 can attenuate bleomycin-induced pulmonary fibrosis by 
      inhibiting the Wnt/beta-catenin pathway in mouse lung fibroblasts.
FAU - Wang, Fangfang
AU  - Wang F
AD  - Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of 
      Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong, China.
FAU - Zhang, Yanan
AU  - Zhang Y
AD  - Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of 
      Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong, China.
FAU - Ren, Jing
AU  - Ren J
AD  - Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of 
      Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong, China.
FAU - Yu, Wencheng
AU  - Yu W
AUID- ORCID: 0000-0003-1134-6843
AD  - Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of 
      Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong, China. 
      ywcheng1167@126.com.
LA  - eng
PT  - Journal Article
DEP - 20220825
PL  - Poland
TA  - Folia Histochem Cytobiol
JT  - Folia histochemica et cytobiologica
JID - 8502651
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (beta Catenin)
RN  - 11056-06-7 (Bleomycin)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.1.- (Hipk2 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Bleomycin/metabolism/toxicity
MH  - Collagen/metabolism
MH  - Fibroblasts/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Serine-Threonine Kinases/genetics
MH  - *Pulmonary Fibrosis/chemically induced/metabolism/pathology
MH  - Transforming Growth Factor beta1/metabolism
MH  - Wnt Signaling Pathway
MH  - beta Catenin
OTO - NOTNLM
OT  - HIPK2
OT  - Wnt/beta-catenin
OT  - XAV939
OT  - mouse
OT  - mouse lung fibroblast
OT  - pulmonary fibrosis
EDAT- 2022/08/26 06:00
MHDA- 2022/10/04 06:00
CRDT- 2022/08/25 04:53
PHST- 2021/12/22 00:00 [received]
PHST- 2022/08/17 00:00 [accepted]
PHST- 2022/08/10 00:00 [revised]
PHST- 2022/08/26 06:00 [pubmed]
PHST- 2022/10/04 06:00 [medline]
PHST- 2022/08/25 04:53 [entrez]
AID - VM/OJS/J/87580 [pii]
AID - 10.5603/FHC.a2022.0022 [doi]
PST - ppublish
SO  - Folia Histochem Cytobiol. 2022;60(3):247-259. doi: 10.5603/FHC.a2022.0022. Epub 
      2022 Aug 25.