PMID- 33319933
OWN - NLM
STAT- MEDLINE
DCOM- 20211014
LR  - 20220716
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 236
IP  - 7
DP  - 2021 Jul
TI  - Distinct effects of pharmacological inhibition of stromelysin1 on 
      endothelial-to-mesenchymal transition and myofibroblast differentiation.
PG  - 5147-5161
LID - 10.1002/jcp.30221 [doi]
AB  - Endothelial-to-mesenchymal transition (EndMT) and fibroblast-to-myofibroblast 
      (FibroMF) differentiation are frequently reported in organ fibrosis. 
      Stromelysin1, a matrix metalloprotease-3 (MMP3) has been indicated in vascular 
      pathologies and organ injuries that often lead to fibrosis. In the current study, 
      we investigated the role of stromelysin1 in EndMT and FibroMF differentiation, 
      which is currently unknown. In our results, whereas TGFbeta2 treatment of 
      endothelial cells (ECs) induced EndMT associated with increased expression of 
      stromelysin1 and mesenchymal markers such as alpha-smooth muscle actin (alphaSMA), 
      N-cadherin, and activin linked kinase-5 (ALK5), inhibition of stromelysin1 
      blunted TGFbeta2-induced EndMT. In contrast, treatment of NIH-3T3 fibroblasts with 
      TGFbeta1 promoted FibroMF differentiation accompanied by increased expression of 
      alphaSMA, N-cadherin, and ALK5. Intriguingly, stromelysin1 inhibition in 
      TGFbeta1-stimulated myofibroblasts further exacerbated fibroproliferation with 
      increased FibroMF marker expression. Gene Expression Omnibus (GEO) data analysis 
      indicated increased stromelysin1 expression associated with EndMT and decreased 
      stromelysin1 expression in human pulmonary fibrosis fibroblasts. In conclusion, 
      our study has identified that EndMT and FibroMF differentiation are reciprocally 
      regulated by stromelysin1.
CI  - (c) 2020 Wiley Periodicals LLC.
FAU - Alharthi, Ahlam
AU  - Alharthi A
AD  - Department of Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, 
      USA.
FAU - Verma, Arti
AU  - Verma A
AD  - Department of Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, 
      USA.
FAU - Sabbineni, Harika
AU  - Sabbineni H
AD  - Department of Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, 
      USA.
FAU - Adil, Mir S
AU  - Adil MS
AD  - Department of Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, 
      USA.
FAU - Somanath, Payaningal R
AU  - Somanath PR
AUID- ORCID: 0000-0003-3017-0230
AD  - Department of Clinical and Experimental Therapeutics, College of Pharmacy, 
      University of Georgia and Charlie Norwood VA Medical Center, Augusta, Georgia, 
      USA.
AD  - Georgia Cancer Center, Medical College of Georgia, Augusta University, Augusta, 
      Georgia, USA.
AD  - Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, 
      Georgia, USA.
AD  - Department of Medicine, Augusta University, Augusta, Georgia, USA.
LA  - eng
GR  - R01 HL103952/HL/NHLBI NIH HHS/United States
GR  - UL1 TR002378/TR/NCATS NIH HHS/United States
GR  - UL1TR002378/TR/NCATS NIH HHS/United States
GR  - R01HL103952/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201215
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (ACTA2 protein, human)
RN  - 0 (Actins)
RN  - 0 (Antigens, CD)
RN  - 0 (CDH2 protein, human)
RN  - 0 (Cadherins)
RN  - 0 (TGFB2 protein, human)
RN  - 0 (Transforming Growth Factor beta2)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 2.7.11.30 (TGFBR1 protein, human)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - 3T3 Cells
MH  - Actins/biosynthesis
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - Cadherins/biosynthesis
MH  - Cell Differentiation/*drug effects
MH  - Cell Line
MH  - Endothelial Cells/metabolism
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Fibroblasts/*cytology
MH  - Fibrosis/pathology
MH  - Humans
MH  - Matrix Metalloproteinase 3/drug effects/*metabolism
MH  - Mice
MH  - Myofibroblasts/*cytology
MH  - Receptor, Transforming Growth Factor-beta Type I/biosynthesis
MH  - Transforming Growth Factor beta2/pharmacology
PMC - PMC8026649
MID - NIHMS1654657
OTO - NOTNLM
OT  - EndMT
OT  - MMP3
OT  - fibrosis
OT  - myofibroblast
OT  - stromelysin1
COIS- Conflict of interest Authors declare that there are no financial or any other 
      conflicts of interest exist.
EDAT- 2020/12/16 06:00
MHDA- 2021/10/15 06:00
PMCR- 2022/07/01
CRDT- 2020/12/15 08:43
PHST- 2020/11/30 00:00 [revised]
PHST- 2019/06/20 00:00 [received]
PHST- 2020/12/03 00:00 [accepted]
PHST- 2020/12/16 06:00 [pubmed]
PHST- 2021/10/15 06:00 [medline]
PHST- 2020/12/15 08:43 [entrez]
PHST- 2022/07/01 00:00 [pmc-release]
AID - 10.1002/jcp.30221 [doi]
PST - ppublish
SO  - J Cell Physiol. 2021 Jul;236(7):5147-5161. doi: 10.1002/jcp.30221. Epub 2020 Dec 
      15.