PMID- 21940816
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20211020
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 46
IP  - 2
DP  - 2012 Feb
TI  - Role of urokinase plasminogen activator receptor-associated protein in mouse 
      lung.
PG  - 233-9
LID - 10.1165/rcmb.2010-0485OC [doi]
AB  - Urokinase plasminogen activator receptor-associated protein (uPARAP, or Endo180) 
      is a transmembrane endocytic receptor that mediates collagen internalization and 
      degradation. uPARAP may be a novel pathway for collagen turnover and matrix 
      remodeling in the lung. The function of uPARAP in lung injury has not been 
      described. We analyzed the pulmonary mechanics of uPARAP(-/-) and wild-type mice 
      at baseline and examined their response after bleomycin instillation. We compared 
      collagen internalization in primary mouse lung fibroblasts (MLFs) from wild-type 
      and uPARAP(-/-) mice using flow cytometry and fluorescent microscopy, and we 
      examined the role of cytokines in regulating uPARAP expression and collagen 
      internalization. We show that uPARAP is highly expressed in the lung, and that 
      uPARAP(-/-) mice have increased lung elastance at baseline and after injury. 
      uPARAP(-/-) mice are protected from changes in lung permeability after acute lung 
      injury and have increased collagen content after bleomycin injury. uPARAP is the 
      primary pathway for internalization of collagens in MLFs. Furthermore, collagen 
      internalization through uPARAP does not require matrix metalloproteinase 
      digestion and is independent of integrins. Mediators of lung injury, including 
      transforming growth factor-beta, TNF-alpha, and IL-1, down-regulate both uPARAP 
      expression and collagen internalization. uPARAP is highly expressed in the murine 
      lung, and loss of uPARAP leads to differences in lung mechanics, lung 
      permeability, and collagen content after injury. uPARAP is required for collagen 
      internalization by MLFs. Thus, uPARAP is a novel pathway that regulates matrix 
      remodeling in the lung after injury.
FAU - Bundesmann, Michael M
AU  - Bundesmann MM
AD  - Pulmonary and Critical Care Medicine, Center for Lung Biology, University of 
      Washington, Seattle, WA 98109, USA.
FAU - Wagner, Teresa E
AU  - Wagner TE
FAU - Chow, Yu-Hua
AU  - Chow YH
FAU - Altemeier, William A
AU  - Altemeier WA
FAU - Steinbach, Trevor
AU  - Steinbach T
FAU - Schnapp, Lynn M
AU  - Schnapp LM
LA  - eng
GR  - F32HL104847/HL/NHLBI NIH HHS/United States
GR  - K24HL068796/HL/NHLBI NIH HHS/United States
GR  - F32 HL104847/HL/NHLBI NIH HHS/United States
GR  - T32 HL07287/HL/NHLBI NIH HHS/United States
GR  - T32 HL007287/HL/NHLBI NIH HHS/United States
GR  - HL083481/HL/NHLBI NIH HHS/United States
GR  - R01 HL083481/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110922
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Receptors, Urokinase Plasminogen Activator)
SB  - IM
MH  - Animals
MH  - Cytokines/physiology
MH  - Down-Regulation
MH  - Flow Cytometry
MH  - Inflammation Mediators/physiology
MH  - Lung/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - Receptors, Urokinase Plasminogen Activator/genetics/*physiology
PMC - PMC3297169
EDAT- 2011/09/24 06:00
MHDA- 2012/03/27 06:00
PMCR- 2013/02/01
CRDT- 2011/09/24 06:00
PHST- 2011/09/24 06:00 [entrez]
PHST- 2011/09/24 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2013/02/01 00:00 [pmc-release]
AID - 2010-0485OC [pii]
AID - 10.1165/rcmb.2010-0485OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2012 Feb;46(2):233-9. doi: 10.1165/rcmb.2010-0485OC. 
      Epub 2011 Sep 22.