Nanodiamonds inhibit scratch-wound repair in lung epithelial cell monolayers by blocking cell migration and inhibiting cell proliferation

Lung cell migration is a crucial step for re-epithelialization that in turn is essential for remodelling and repair after lung injury. In the present paper we hypothesize that secreted ATX (autotaxin), which exhibits lysoPLD (lysophospholipase D) activity, stimulates lung epithelial cell migration through LPA (lysophosphatidic acid) generation-dependent and -independent pathways. Release of endogenous ATX protein and activity was detected in lung epithelial cell culture medium. ATX with V5 tag overexpressed conditional medium had higher LPA levels compared with control medium and stimulated cell migration through Gαi-coupled LPA receptors, cytoskeleton rearrangement, phosphorylation of PKC (protein kinase C) δ and cortactin at the leading edge of migrating cells. Inhibition of PKCδ attenuated ATX–V5 overexpressed conditional medium-mediated phosphorylation of cortactin. In addition, a recombinant ATX mutant, lacking lysoPLD activity, or heat-inactived ATX also induced lung epithelial cell migration. Extracelluar ATX bound to the LPA receptor and integrin β4 complex on A549 cell surface. Finally, intratracheal administration of LPS (lipopolysaccharide) into the mouse airway induced ATX release and LPA production in BAL (bronchoalveolar lavage) fluid. These results suggested a significant role for ATX in lung epithelial cell migration and remodelling through its ability to induce LPA production-mediated phosphorylation of PKCδ and cortactin. In addition we also demonstrated assocation of ATX with the epithelial cell-surface LPA receptor and integrin β4.

Download Full-text

THE ROLE OF FIBROBLAST TRANSDIFFERENTIATION IN LUNG EPITHELIAL CELL PROLIFERATION, DIFFERENTIATION, AND REPAIR IN VITRO

Pediatric Pathology & Molecular Medicine ◽

10.1080/15227950307732 ◽

2003 ◽

Vol 22 (3) ◽

pp. 189-207 ◽

Cited By ~ 40

Author(s):

J. S. Torday ◽

E. Torres ◽

V. K. Rehan

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Lung Epithelial Cell ◽

Epithelial Cell Proliferation ◽

Lung Epithelial

Download Full-text

Cross-talk between lysophosphatidic acid receptor 1 and tropomyosin receptor kinase A promotes lung epithelial cell migration

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ◽

10.1016/j.bbamcr.2015.11.012 ◽

2016 ◽

Vol 1863 (2) ◽

pp. 229-235 ◽

Cited By ~ 3

Author(s):

Ling Nan ◽

Jianxin Wei ◽

Anastasia M. Jacko ◽

Miranda K. Culley ◽

Jing Zhao ◽

...

Keyword(s):

Cell Migration ◽

Epithelial Cell ◽

Lysophosphatidic Acid ◽

Cross Talk ◽

Lung Epithelial Cell ◽

Receptor Kinase ◽

Acid Receptor ◽

Epithelial Cell Migration ◽

Lung Epithelial ◽

Kinase A

Download Full-text

Oxidative stress destabilizes protein arginine methyltransferase 4 via glycogen synthase kinase 3β to impede lung epithelial cell migration

AJP Cell Physiology ◽

10.1152/ajpcell.00073.2017 ◽

2017 ◽

Vol 313 (3) ◽

pp. C285-C294 ◽

Cited By ~ 4

Author(s):

Xiuying Li ◽

Yandong Lai ◽

Jin Li ◽

Mingyi Zou ◽

Chunbin Zou

Keyword(s):

Oxidative Stress ◽

Cell Migration ◽

Epithelial Cell ◽

Glycogen Synthase ◽

Lung Epithelial Cell ◽

Glycogen Synthase Kinase 3Β ◽

Arginine Methyltransferase ◽

Epithelial Cell Migration ◽

Lung Epithelial ◽

Gsk 3Β

Oxidative stress impacts normal cellular function leading to the pathogenesis of various diseases including pulmonary illnesses. Protein arginine methyltransferase 4 (PRMT4) is critical for normal lung alveolar epithelial cell development; however, the regulation of PRMT4 within such pulmonary diseases has yet to be elucidated. Using biochemical approaches, we uncovered that peroxide (H2O2) treatment decreases PRMT4 protein stability in murine lung epithelial (MLE12) cells to impede cell migration. Protein kinase glycogen synthase kinase 3β (GSK-3β) interacts with PRMT4 and catalyzes PRMT4 T132 phosphorylation that protects PRMT4 from ubiquitin proteasomal degradation. H2O2 downregulates GSK-3β to reduce PRMT4 at protein level. PRMT4 promotes cell migration and H2O2 degrades PRMT4 to inhibit lung epithelial cell migration. These observations demonstrate that oxidative stress destabilizes PRMT4 via GSK-3β signaling to impede lung epithelial cell migration that may hinder the lung repair and regeneration process.

Download Full-text