PMID- 15895394
OWN - NLM
STAT- MEDLINE
DCOM- 20060111
LR  - 20220310
IS  - 0021-9541 (Print)
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 205
IP  - 3
DP  - 2005 Dec
TI  - Induction of TGF-beta1 in the trabecular meshwork under cyclic mechanical stress.
PG  - 364-71
AB  - The pathophysiological mechanisms involved in the failure of the trabecular 
      meshwork (TM) to maintain normal levels of aqueous outflow in glaucoma are not 
      yet understood. Aberrant activation of the transforming growth factor beta-1 
      (TGF-beta1) pathway has been implicated in several degenerative diseases. We 
      investigated the possibility that chronic cyclic mechanical stress that affects 
      the TM might result in increased production of TGF-beta1. Primary cultures of TM 
      cells subjected to cyclic mechanical stress (5% stretching, 1 cycle/sec) 
      demonstrate a significant increase in total and biologically active secreted 
      TGF-beta1 that was associated with activation of the TGF-beta1 promoter, measured 
      using a recombinant adenovirus expressing the secreted reporter gene secreted 
      alkaline phosphatase protein (SEAP) under the TGF-beta1 gene promoter 
      (AdTGFbeta1-SEAP). Associated changes in the transcription of MMP-2, TIMP-2, and 
      CTGF were assessed by semiquantitative PCR. Immunohistochemical analysis of 
      TGF-beta1 in organ culture of human eyes revealed a generalized accumulation of 
      this protein in the extracellular matrix (ECM) of the TM, while expression of the 
      TGF-beta1 promoter, analyzed using the LacZ reporter gene, was localized in some 
      specific cells within the outflow pathway. Induction of the TGF-beta1 promoter in 
      organ culture was demonstrated using a novel model for cyclic mechanical stress 
      in human perfused anterior segments infected with AdTGFbeta1-SEAP. Given the 
      relevant physiological and pathophysiological roles of TGF-beta1, its induction 
      after cyclic mechanical stress in the TM supports the hypothesis that this 
      cytokine might play a significant role in the physiology of the TM, and 
      contribute to the pathological changes of this tissue in certain forms of 
      glaucoma.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Liton, P B
AU  - Liton PB
AD  - Department of Ophthalmology, Duke University Eye Center, Durham, NC 27710, USA.
FAU - Liu, X
AU  - Liu X
FAU - Challa, P
AU  - Challa P
FAU - Epstein, D L
AU  - Epstein DL
FAU - Gonzalez, P
AU  - Gonzalez P
LA  - eng
GR  - P30 EY005722/EY/NEI NIH HHS/United States
GR  - R01 EY016228-01A1/EY/NEI NIH HHS/United States
GR  - EY05722/EY/NEI NIH HHS/United States
GR  - 1K23EY014019-01A1/EY/NEI NIH HHS/United States
GR  - K23 EY014019/EY/NEI NIH HHS/United States
GR  - EY01894/EY/NEI NIH HHS/United States
GR  - R01 EY001894/EY/NEI NIH HHS/United States
GR  - R01 EY016228/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Anterior Eye Segment/metabolism
MH  - Cells, Cultured
MH  - Extracellular Matrix/metabolism
MH  - Humans
MH  - In Vitro Techniques
MH  - Perfusion
MH  - Promoter Regions, Genetic
MH  - Stress, Mechanical
MH  - Trabecular Meshwork/*metabolism
MH  - Transforming Growth Factor beta/*biosynthesis/genetics/metabolism/physiology
MH  - Transforming Growth Factor beta1
PMC - PMC3143836
MID - NIHMS311635
EDAT- 2005/05/17 09:00
MHDA- 2006/01/13 09:00
PMCR- 2011/07/26
CRDT- 2005/05/17 09:00
PHST- 2005/05/17 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/05/17 09:00 [entrez]
PHST- 2011/07/26 00:00 [pmc-release]
AID - 10.1002/jcp.20404 [doi]
PST - ppublish
SO  - J Cell Physiol. 2005 Dec;205(3):364-71. doi: 10.1002/jcp.20404.