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Deletion of scap alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts

Deletion of scap alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts
Deletion of scap alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts
Pulmonary function after birth is dependent upon surfactant lipids that reduce surface tension in the alveoli. The sterol-responsive element-binding proteins (SREBPs) are transcription factors regulating expression of genes controlling lipid homeostasis in many tissues. To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (ScapDelta/Delta) in vivo. Prior to birth (E18.5), deletion of Scap decreased the expression of both SREBPs and a number of genes regulating fatty acid and cholesterol metabolism. Nevertheless, ScapDelta/Delta mice survived postnatally, surfactant and lung tissue lipids being substantially normalized in adult ScapDelta/Delta mice. Although phospholipid synthesis was decreased in type II cells from adult ScapDelta/Delta mice, lipid storage, synthesis, and transfer by lung lipofibroblasts were increased. mRNA microarray data indicated that SCAP influenced two major gene networks, one regulating lipid metabolism and the other stress-related responses. Deletion of the SCAP/SREBP pathway in respiratory epithelial cells altered lung lipid homeostasis and induced compensatory lipid accumulation and synthesis in lung lipofibroblasts
0021-9258
4018-4030
Besnard, Valerie
39b843ae-0b82-440e-8bfc-191cf6d8619c
Wert, Susan E.
cdc863a5-5f42-47fd-af49-fb1e10dab174
Stahlman, Mildred T.
58cc1067-a244-4e7f-8124-60e8bc92b93a
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Xu, Yan
2b4952f1-3855-4a5d-a8b0-777561a292e1
Ikegami, Machiko
24da55aa-037b-4900-b817-691033d39ffc
Whitsett, Jeffrey A.
84fb8fc3-212e-4741-8934-d4083cd6549b
Besnard, Valerie
39b843ae-0b82-440e-8bfc-191cf6d8619c
Wert, Susan E.
cdc863a5-5f42-47fd-af49-fb1e10dab174
Stahlman, Mildred T.
58cc1067-a244-4e7f-8124-60e8bc92b93a
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Xu, Yan
2b4952f1-3855-4a5d-a8b0-777561a292e1
Ikegami, Machiko
24da55aa-037b-4900-b817-691033d39ffc
Whitsett, Jeffrey A.
84fb8fc3-212e-4741-8934-d4083cd6549b

Besnard, Valerie, Wert, Susan E., Stahlman, Mildred T., Postle, Anthony D., Xu, Yan, Ikegami, Machiko and Whitsett, Jeffrey A. (2009) Deletion of scap alveolar type II cells influences lung lipid homeostasis and identifies a compensatory role for pulmonary lipofibroblasts. The Journal of Biological Chemistry, 286 (6), 4018-4030. (doi:10.1074/jbc.M805388200). (PMID:19074148)

Record type: Article

Abstract

Pulmonary function after birth is dependent upon surfactant lipids that reduce surface tension in the alveoli. The sterol-responsive element-binding proteins (SREBPs) are transcription factors regulating expression of genes controlling lipid homeostasis in many tissues. To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (ScapDelta/Delta) in vivo. Prior to birth (E18.5), deletion of Scap decreased the expression of both SREBPs and a number of genes regulating fatty acid and cholesterol metabolism. Nevertheless, ScapDelta/Delta mice survived postnatally, surfactant and lung tissue lipids being substantially normalized in adult ScapDelta/Delta mice. Although phospholipid synthesis was decreased in type II cells from adult ScapDelta/Delta mice, lipid storage, synthesis, and transfer by lung lipofibroblasts were increased. mRNA microarray data indicated that SCAP influenced two major gene networks, one regulating lipid metabolism and the other stress-related responses. Deletion of the SCAP/SREBP pathway in respiratory epithelial cells altered lung lipid homeostasis and induced compensatory lipid accumulation and synthesis in lung lipofibroblasts

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More information

e-pub ahead of print date: 11 December 2008
Published date: 6 February 2009
Organisations: Infection Inflammation & Immunity

Identifiers

Local EPrints ID: 72677
URI: http://eprints.soton.ac.uk/id/eprint/72677
ISSN: 0021-9258
PURE UUID: 79974230-3d3b-497b-8cb1-812455b18c4e
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

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Date deposited: 19 Feb 2010
Last modified: 14 Mar 2024 02:31

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Contributors

Author: Valerie Besnard
Author: Susan E. Wert
Author: Mildred T. Stahlman
Author: Yan Xu
Author: Machiko Ikegami
Author: Jeffrey A. Whitsett

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