PMID- 35231032
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20220310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 17
IP  - 3
DP  - 2022
TI  - Hypoxia-induced interstitial transformation of microvascular endothelial cells by 
      mediating HIF-1alpha/VEGF signaling in systemic sclerosis.
PG  - e0263369
LID - 10.1371/journal.pone.0263369 [doi]
LID - e0263369
AB  - OBJECTIVE: The aim of this research was to systematically investigate the effects 
      of endothelial mesenchymal transition (EndMT) induced by hypoxia on the skin 
      microvascular remodeling of systemic sclerosis (SSc) and the underlying 
      mechanism. METHODS: Skin tissues from SSc patients and controls were collected 
      for isobaric tags for the relative and absolute quantification (iTRAQ)-based 
      proteomics and immunohistochemical test. Human microvascular endothelial cell 
      line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen 
      or bevacizumab. RESULTS: The iTRAQ-based proteomics indicated a significantly 
      upregulated hypoxia-inducible factor-1 (HIF-1) signal in SSc samples. The 
      immunohistochemical results demonstrated the significant downregulation of CD31, 
      the positive staining of alpha-smooth muscle actin (alpha-SMA), HIF-1alpha, and vascular 
      endothelial growth factor (VEGF-a) in SSc skin tissues, compared with control 
      samples. Consistent with these observations, HMEC-1 cells cultured under hypoxic 
      conditions exhibited a significant decrease in CD31 and VE-cadherin expression, 
      alongside a marked increase in the expression of alpha-SMA and fibronectin, as well 
      as a distinct upregulation of HIF-1alpha and VEGF-a, when compared with those under 
      normal conditions. It is noteworthy that the inhibition of HIF-1alpha by tamoxifen 
      effectively downregulated the hypoxic induction of VEGF-a and alpha-SMA while 
      rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor 
      bevacizumab treatment had the same effect on the hypoxic expression of alpha-SMA and 
      CD31, as a tamoxifen intervention, but did not reduce HIF-1alpha. CONCLUSION: These 
      results suggest that the HIF-1alpha/VEGF signaling pathway can have a critical role 
      in mediating the effect of hypoxia-induced EndMT on the skin microvascular 
      remodeling of SSc.
FAU - Mao, Jing
AU  - Mao J
AD  - Department of Dermatology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, P.R. China.
FAU - Liu, Jiexiong
AU  - Liu J
AD  - Department of Dermatology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, P.R. China.
FAU - Zhou, Mei
AU  - Zhou M
AD  - Department of Dermatology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, P.R. China.
FAU - Wang, Guiqiang
AU  - Wang G
AD  - Department of Infectious Disease, Peking University First Hospital, Beijing, 
      China.
FAU - Xiong, Xia
AU  - Xiong X
AD  - Department of Dermatology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, P.R. China.
FAU - Deng, Yongqiong
AU  - Deng Y
AUID- ORCID: 0000-0003-2023-830X
AD  - Department of Dermatology, The Affiliated Hospital of Southwest Medical 
      University, Luzhou, Sichuan, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220301
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - *Vascular Endothelial Growth Factor A
PMC - PMC8887755
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/03/02 06:00
MHDA- 2022/03/11 06:00
PMCR- 2022/03/01
CRDT- 2022/03/01 17:12
PHST- 2021/02/25 00:00 [received]
PHST- 2022/01/18 00:00 [accepted]
PHST- 2022/03/01 17:12 [entrez]
PHST- 2022/03/02 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2022/03/01 00:00 [pmc-release]
AID - PONE-D-21-05697 [pii]
AID - 10.1371/journal.pone.0263369 [doi]
PST - epublish
SO  - PLoS One. 2022 Mar 1;17(3):e0263369. doi: 10.1371/journal.pone.0263369. 
      eCollection 2022.