PMID- 38252666
OWN - NLM
STAT- MEDLINE
DCOM- 20240307
LR  - 20240307
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 326
IP  - 3
DP  - 2024 Mar 1
TI  - Role of ZIP kinase in development of myofibroblast differentiation from HPMCs.
PG  - L353-L366
LID - 10.1152/ajplung.00251.2023 [doi]
AB  - During the development of pleural fibrosis, pleural mesothelial cells (PMCs) 
      undergo phenotypic switching from differentiated mesothelial cells to mesenchymal 
      cells (MesoMT). Here, we investigated how external stimuli such as TGF-beta induce 
      HPMC-derived myofibroblast differentiation to facilitate the development of 
      pleural fibrosis. TGF-beta significantly increased di-phosphorylation but not 
      mono-phosphorylation of myosin II regulatory light chain (RLC) in HPMCs. An 
      increase in RLC di-phosphorylation was also found at the pleural layer of our 
      carbon black bleomycin (CBB) pleural fibrosis mouse model, where it showed 
      filamentous localization that coincided with alpha smooth muscle actin (alphaSMA) in 
      the cells in the pleura. Among the protein kinases that can phosphorylate myosin 
      II RLC, ZIPK (zipper-interacting kinase) protein expression was significantly 
      augmented after TGF-beta stimulation. Furthermore, ZIPK gene silencing attenuated 
      RLC di-phosphorylation, suggesting that ZIPK is responsible for 
      di-phosphorylation of myosin II in HPMCs. Although TGF-beta significantly increased 
      the expression of ZIP kinase protein, the change in ZIP kinase mRNA was marginal, 
      suggesting a posttranscriptional mechanism for the regulation of ZIP kinase 
      expression by TGF-beta. ZIPK gene knockdown (KD) also significantly reduced 
      TGF-beta-induced upregulation of alphaSMA expression. This finding suggests that siZIPK 
      attenuates myofibroblast differentiation of HPMCs. siZIPK diminished 
      TGF-beta-induced contractility of HPMCs consistent with siZIPK-induced decrease in 
      the di-phosphorylation of myosin II RLC. The present results implicate ZIPK in 
      the regulation of the contractility of HPMC-derived myofibroblasts, phenotype 
      switching, and myofibroblast differentiation of HPMCs.NEW & NOTEWORTHY Here, we 
      highlight that ZIP kinase is responsible for di-phosphorylation of myosin light 
      chain, which facilitates stress fiber formation and actomyosin-based cell 
      contraction during mesothelial to mesenchymal transition in human pleural 
      mesothelial cells. This transition has a significant impact on tissue remodeling 
      and subsequent stiffness of the pleura. This study provides insight into a new 
      therapeutic strategy for the treatment of pleural fibrosis.
FAU - Choo, Young-Yeon
AU  - Choo YY
AUID- ORCID: 0000-0001-5288-1186
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Sakai, Tsuyoshi
AU  - Sakai T
AUID- ORCID: 0000-0002-2153-0831
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Ikebe, Reiko
AU  - Ikebe R
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Jeffers, Ann
AU  - Jeffers A
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Idell, Steven
AU  - Idell S
AUID- ORCID: 0000-0003-4389-2152
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Tucker, Torry A
AU  - Tucker TA
AUID- ORCID: 0000-0002-0823-3234
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
FAU - Ikebe, Mitsuo
AU  - Ikebe M
AUID- ORCID: 0000-0002-8299-6643
AD  - Department of Cellular and Molecular Biology, The University of Texas at Tyler 
      Health Science Center, Tyler, Texas, United States. ROR: 
      https://ror.org/01sps7q28
LA  - eng
GR  - HL142853/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
PT  - Journal Article
DEP - 20240122
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - EC 2.7.11.1 (Death-Associated Protein Kinases)
RN  - 0 (Myosin Light Chains)
RN  - EC 3.6.1.- (Myosin Type II)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Humans
MH  - Death-Associated Protein Kinases/genetics/metabolism
MH  - *Myofibroblasts/metabolism
MH  - Phosphorylation
MH  - Myosin Light Chains/metabolism
MH  - *Pleural Diseases/metabolism
MH  - Myosin Type II/metabolism
MH  - Transforming Growth Factor beta/pharmacology/metabolism
MH  - Fibrosis
OTO - NOTNLM
OT  - ZIP kinase
OT  - lung mesothelial cells
OT  - myosin light chain phosphorylation
OT  - pleural fibrosis
OT  - stress fiber
EDAT- 2024/01/22 18:42
MHDA- 2024/03/07 06:43
CRDT- 2024/01/22 13:35
PHST- 2024/03/07 06:43 [medline]
PHST- 2024/01/22 18:42 [pubmed]
PHST- 2024/01/22 13:35 [entrez]
AID - 10.1152/ajplung.00251.2023 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2024 Mar 1;326(3):L353-L366. doi: 
      10.1152/ajplung.00251.2023. Epub 2024 Jan 22.