PMID- 8587235
OWN - NLM
STAT- MEDLINE
DCOM- 19960327
LR  - 20190725
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 48
IP  - 6
DP  - 1995 Dec
TI  - Transfer of a mutated gene encoding active transforming growth factor-beta 1 
      suppresses mitogenesis and IL-1 response in the glomerulus.
PG  - 1747-57
AB  - Using in vivo gene transfer, we examined the anti-inflammatory potential of 
      transforming growth factor-beta 1 (TGF-beta 1) in the renal glomerulus. TGF-beta 
      1 cDNA, modified to allow for secretion of the active form of TGF-beta 1, was 
      introduced into cultured rat mesangial cells. The responses of the established 
      transfectants were examined in culture. In vitro, the transduced mesangial cells 
      showed a reduced mitogenic response to fetal calf serum and were insensitive to 
      induction of matrix metalloproteinase-9 (MMP-9) by the proinflammatory cytokine 
      IL-1 beta. To examine whether glomeruli which express active TGF-beta 1 in vivo 
      are insensitive to these same stimuli, TGF-beta transfectants were transferred 
      into normal rat glomeruli via renal artery injection. After 24 hours, isolated 
      glomeruli containing transfectants exhibited TGF-beta bioactivity, a reduced 
      mitogenic response, and repressed expression of MMP-9 in response to IL-1 beta. 
      We further examined the responses of these chimeric glomeruli to an in vivo 
      mitogenic stimulus by transferring TGF-beta transfectants into glomeruli of 
      kidneys one day after the induction of anti-Thy-1 nephritis. The mitogenic 
      activity of isolated glomeruli was examined four days after the cell injection. 
      Compared to unmodified or mock cell-containing glomeruli, the in vivo mitogenic 
      activity of glomeruli containing TGF-beta transfectants was significantly 
      repressed. Furthermore, cellular outgrowth from nephritic glomeruli expressing 
      active TGF-beta 1 was also suppressed ex vivo compared to controls. These data 
      indicate that TGF-beta 1 inhibits mitogenesis and IL-1 response of the glomerulus 
      and may, in part, act as a potential early suppressor of glomerular inflammation.
FAU - Kitamura, M
AU  - Kitamura M
AD  - Department of Medicine, University College London Medical School, England, United 
      Kingdom.
FAU - Burton, S
AU  - Burton S
FAU - English, J
AU  - English J
FAU - Kawachi, H
AU  - Kawachi H
FAU - Fine, L G
AU  - Fine LG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 3.4.24.- (Metalloendopeptidases)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cells, Cultured
MH  - *Gene Transfer Techniques
MH  - Glomerular Mesangium/cytology/*physiology
MH  - Interleukin-1/metabolism/*physiology
MH  - Male
MH  - Metalloendopeptidases/metabolism
MH  - Mitosis/*physiology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Inbred F344
MH  - Transforming Growth Factor beta/genetics/*physiology
EDAT- 1995/12/01 00:00
MHDA- 1995/12/01 00:01
CRDT- 1995/12/01 00:00
PHST- 1995/12/01 00:00 [pubmed]
PHST- 1995/12/01 00:01 [medline]
PHST- 1995/12/01 00:00 [entrez]
AID - S0085-2538(15)59245-4 [pii]
AID - 10.1038/ki.1995.473 [doi]
PST - ppublish
SO  - Kidney Int. 1995 Dec;48(6):1747-57. doi: 10.1038/ki.1995.473.