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Insights in Enzyme Research
ISSN: 2573-4466
E u r o S c i C o n C o n g r e s s o n
Enzymology and
Molecular Biology
A u g u s t 1 3 - 1 4 , 2 0 1 8
P a r i s , F r a n c e
Enzymology 2018
I
diopathic pulmonary fibrosis (IPF) is a pernicious lung disease characterized by alveolar epithelial apoptosis, dysregulated
repair of epithelial injury, scar formation and respiratory failure. Currently there are only two FDA approved drugs for IPF; which
do not cure the disease, but just slow the progression of disease, there is a need to identify new therapeutic targets for the
disease. Phospholipase D (PLD), an important lipid mediator involved in several pathophysiologies, catalyzes the hydrolysis
of phosphatidylcholine, generating phosphatidic acid (PA) and choline. PLD mediated PA generation is involved in regulation
of various cellular processes including cell survival, cell migration, cell proliferation, differentiation, cytoskeletal changes,
membrane trafficking, and autophagy. In this study, we have identified phospholipase D (PLD) generated phosphatidic acid (PA)
signalling in the development of pulmonary fibrosis (PF). Phospholipase D (PLD), an important lipid mediator involved in several
pathophysiologies, catalyses the hydrolysis of phosphatidylcholine, generating phosphatidic acid (PA) and choline. Of the PLD
isoenzymes, the protein expression of PLD2, but not PLD1, was up-regulated in lung tissues from IPF patients and bleomycin
challengedmice. Both PLD2 (Pld2
-/-
) and PLD1 (Pld1
-/-
) deficient micewere protected against bleomycin induced lung inflammation
and fibrosis, thereby establishing the role of PLD in fibrogenesis. To further understand how PLD mediates epithelial injury during
PF, challenging of bronchial airway epithelial cells (Beas2B) with bleomycin stimulated PLD activity and PLD2 expression in the
cells. Further, inhibition of PLD2 with VU0364739 attenuated bleomycin-induced mitochondrial (mt) superoxide production and
mtDNA damage that leads to apoptosis in Beas2B cells. These results support a critical role for PLD2 signalling in promoting
pulmonary fibrosis in humans and mice. We reason that PLD2 may be a novel therapeutic target in mitigating IPF.
vsurya2@uic.eduPhospholipase D inhibition mitigates pulmonary fibrosis by
attenuating bronchial epithelial cell mitochondrial DNA
damage and apoptosis
Vidyani Suryadevara
1
, Longshuang Huang
1
, Seok-Jo-Kim
2,3
,
Panfeng Fu
1
, Carol Feghali- Bostwick
4
, Gilbert Di Paolo
5
, David
W Kamp
2,3
and Viswanathan Natarajan
1
1
University of Illinois at Chicago, Chicago, Illinois
2
Northwestern University Feinberg School of Medicine, Chicago Illinois
3
Jesse Brown VA Medical Center, Chicago, Illinois
4
Medical University of South Carolina, Charleston, South Carolina
5
Columbia University Medical Center, New York
Insights Enzyme Res 2018, Volume 2
DOI: 10.21767/2573-4466-C1-003