Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 278.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26186947
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Lung+Cell+Mol+Physiol
2015 ; 309
(6
): L507-25
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Lost after translation: insights from pulmonary surfactant for understanding the
role of alveolar epithelial dysfunction and cellular quality control in fibrotic
lung disease
#MMPMID26186947
Mulugeta S
; Nureki S
; Beers MF
Am J Physiol Lung Cell Mol Physiol
2015[Sep]; 309
(6
): L507-25
PMID26186947
show ga
Dating back nearly 35 years ago to the Witschi hypothesis, epithelial cell
dysfunction and abnormal wound healing have reemerged as central concepts in the
pathophysiology of idiopathic pulmonary fibrosis (IPF) in adults and in
interstitial lung disease in children. Alveolar type 2 (AT2) cells represent a
metabolically active compartment in the distal air spaces responsible for
pulmonary surfactant biosynthesis and function as a progenitor population
required for maintenance of alveolar integrity. Rare mutations in surfactant
system components have provided new clues to understanding broader questions
regarding the role of AT2 cell dysfunction in the pathophysiology of fibrotic
lung diseases. Drawing on data generated from a variety of model systems
expressing disease-related surfactant component mutations [surfactant proteins A
and C (SP-A and SP-C); the lipid transporter ABCA3], this review will examine the
concept of epithelial dysfunction in fibrotic lung disease, provide an update on
AT2 cell and surfactant biology, summarize cellular responses to mutant
surfactant components [including endoplasmic reticulum (ER) stress, mitochondrial
dysfunction, and intrinsic apoptosis], and examine quality control pathways
(unfolded protein response, the ubiquitin-proteasome system, macroautophagy) that
can be utilized to restore AT2 homeostasis. This integrated response and its
derangement will be placed in the context of cell stress and quality control
signatures found in patients with familial or sporadic IPF as well as
non-surfactant-related AT2 cell dysfunction syndromes associated with a fibrotic
lung phenotype. Finally, the need for targeted therapeutic strategies for
pulmonary fibrosis that address epithelial ER stress, its downstream signaling,
and cell quality control are discussed.