PMID- 18642127
OWN - NLM
STAT- MEDLINE
DCOM- 20090928
LR  - 20211020
IS  - 1617-7940 (Electronic)
IS  - 1617-7959 (Print)
IS  - 1617-7940 (Linking)
VI  - 8
IP  - 4
DP  - 2009 Aug
TI  - Collagen-related gene and protein expression changes in the lung in response to 
      chronic hypoxia.
PG  - 263-72
LID - 10.1007/s10237-008-0133-2 [doi]
AB  - Collagen accumulation likely contributes to increased vascular and airway 
      impedance in hypoxia-induced pulmonary hypertension (HPH). Collagen exists in 
      multiple subtypes and can accumulate via increased synthesis or decreased 
      degradation. To better understand the individual contributions of fibrillar (FB) 
      and basement membrane (BM) collagen, matrix metalloproteinases (MMPs) and tissue 
      inhibitors of MMPs (TIMPs) to pulmonary vascular and airway remodeling in HPH, we 
      investigated the temporal changes in gene and protein expression in the lungs of 
      mice exposed to hypoxia for 0, 3, 6, 10 and 15 days. The earliest and largest 
      change in gene expression was of type I FB collagen, which was significantly 
      increased over control levels at 6, 10 and 15 days of hypoxia (p < 0.05). Type 
      III FB and type IV BM collagen were increased at 10 and 15 days of hypoxia (p < 
      0.05); MMP and TIMP gene expression levels were typically higher but sometimes 
      lower than control levels at various time points. Collagen protein content was 
      increased in whole lungs as early as 6 days of hypoxia and increased 
      monotonically with longer exposures. However, neither qualitative nor 
      semi-quantitative analysis of immunohistochemistry demonstrated accumulation of 
      type I FB collagen in compartments of the lung other than large airways, 
      suggesting that other collagen subtypes may be important contributors to collagen 
      protein accumulation. These results provide insight into the patterns of gene and 
      protein expression relevant to collagen accumulation in the lung in response to 
      chronic hypoxia, through which we can develop a better understanding of the time 
      course of changes in matrix biology and biomechanics that occur in HPH.
FAU - Estrada, Kristine D
AU  - Estrada KD
AD  - Biomedical Engineering Department, University of Wisconsin, Madison, Madison, WI 
      53706-1609, USA.
FAU - Chesler, Naomi C
AU  - Chesler NC
LA  - eng
GR  - R01 HL086939/HL/NHLBI NIH HHS/United States
GR  - R01 HL086939-01A1/HL/NHLBI NIH HHS/United States
GR  - R01 HL086939-02/HL/NHLBI NIH HHS/United States
GR  - R01HL086939/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080720
PL  - Germany
TA  - Biomech Model Mechanobiol
JT  - Biomechanics and modeling in mechanobiology
JID - 101135325
RN  - 9007-34-5 (Collagen)
RN  - RMB44WO89X (Hydroxyproline)
SB  - IM
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Collagen/*metabolism
MH  - Extracellular Matrix/metabolism
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation
MH  - Hydroxyproline/metabolism
MH  - Hypertension, Pulmonary/metabolism
MH  - *Hypoxia
MH  - Immunohistochemistry/methods
MH  - Lung/embryology/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Time Factors
PMC - PMC2718063
MID - NIHMS60119
EDAT- 2008/07/22 09:00
MHDA- 2009/09/29 06:00
PMCR- 2009/08/01
CRDT- 2008/07/22 09:00
PHST- 2007/06/28 00:00 [received]
PHST- 2008/07/06 00:00 [accepted]
PHST- 2008/07/22 09:00 [pubmed]
PHST- 2009/09/29 06:00 [medline]
PHST- 2008/07/22 09:00 [entrez]
PHST- 2009/08/01 00:00 [pmc-release]
AID - 10.1007/s10237-008-0133-2 [doi]
PST - ppublish
SO  - Biomech Model Mechanobiol. 2009 Aug;8(4):263-72. doi: 10.1007/s10237-008-0133-2. 
      Epub 2008 Jul 20.