PMID- 1940433
OWN - NLM
STAT- MEDLINE
DCOM- 19911127
LR  - 20190723
IS  - 0022-202X (Print)
IS  - 0022-202X (Linking)
VI  - 97
IP  - 4
DP  - 1991 Oct
TI  - Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts.
PG  - 634-7
AB  - In this report, we have investigated the secretion and synthesis of transforming 
      growth factor-beta 1 (TGF-beta 1) by human dermal fibroblast cultures in response 
      to hypoxia (2% oxygen), and have compared it to standard oxygen culture 
      conditions (15% oxygen at the cell surface). Sandwich enzyme-linked immunosorbent 
      assay (SELISA) showed a selective and progressive increase in secretion of the 
      TGF-beta 1 isoform in response to hypoxia, up to ninefold after cultures were 
      exposed to low oxygen for 72 h; TGF-beta 2 peptide levels were not increased. We 
      then investigated the transcriptional regulation of the TGF-beta 1 gene in 
      response to low and standard oxygen tensions. In the first 24-48 h, TGF-beta 1 
      mRNA levels decreased steadily in both oxygen environments. This mRNA decline 
      continued for up to 72 h in standard oxygen but not in cultures exposed to low 
      oxygen tension. At 72 h, steady-state TGF-beta 1 mRNA levels were 8 times greater 
      in low compared to standard oxygen, and this increase was reversible upon 
      re-exposure of fibroblast cultures to standard oxygen tension for 24 h. Elevated 
      TGF-beta 1 m-RNA levels in both low and standard oxygen declined steadily and 
      with the same half-life after the addition of actinomycin D, suggesting that 
      hypoxia increased TGF-beta 1 transcription rather than mRNA stability. We 
      conclude that low oxygen tension upregulates the synthesis of TGF-beta 1 by human 
      dermal fibroblasts, and leads to increased secretion of this peptide.
FAU - Falanga, V
AU  - Falanga V
AD  - University of Miami School of Medicine, Department of Dermatology and Cutaneous 
      Surgery, Florida, 33101.
FAU - Qian, S W
AU  - Qian SW
FAU - Danielpour, D
AU  - Danielpour D
FAU - Katz, M H
AU  - Katz MH
FAU - Roberts, A B
AU  - Roberts AB
FAU - Sporn, M B
AU  - Sporn MB
LA  - eng
GR  - AR 39658/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - *Cell Hypoxia
MH  - Cells, Cultured
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - RNA, Messenger/analysis
MH  - Skin/*metabolism
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/*biosynthesis
MH  - Up-Regulation
EDAT- 1991/10/01 00:00
MHDA- 1991/10/01 00:01
CRDT- 1991/10/01 00:00
PHST- 1991/10/01 00:00 [pubmed]
PHST- 1991/10/01 00:01 [medline]
PHST- 1991/10/01 00:00 [entrez]
AID - S0022-202X(91)90300-F [pii]
AID - 10.1111/1523-1747.ep12483126 [doi]
PST - ppublish
SO  - J Invest Dermatol. 1991 Oct;97(4):634-7. doi: 10.1111/1523-1747.ep12483126.