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E R Tamm

Publications and source records attributed to E R Tamm.

At least 19 recordsLinked to original sources
PubMed2002

[The role of myocilin in the pathogenesis of primary open-angle glaucoma].

Mutations in myocilin are responsible for autosomal-dominant inherited juvenile open-angle glaucoma and some subgroups of adult-onset glaucoma (POAG). Myocilin is a secreted glycoprotein with a molecular weight of approximately 55-57 kDa that forms dimers and multimers. Structural motives are domains that have similarities with myosin and olfactomedin, a signalling sequence as well as a leucine zipper at the N-terminus of myocilin. Most mutations that were identified in patients with POAG are localized in the olfactomedin domain which is highly conserved between species. In the eye, myocilin is highly expressed in the trabecular meshwork (TM), the sclera, the ciliary body and the iris, lower amounts are seen in the retina and the optic nerve. In addition, secreted myocilin is detected in the aqueous humor. In the chamber angle, myocilin is associated with fibrillar components of the extracellular matrix in the cribriform portion of the TM. Myocilin binds specifically to the HepII domain of fibronectin. In organ cultures of perfused anterior eye segments, recombinant myocilin increases outflow resistance. In cultured TM cells, myocilin is induced by treatment with dexamethasone in a similar time course as observed in steroid-induced glaucoma. Myocilin is also induced by transforming growth factor-beta (TGF-beta) and mechanical stress. Mice with a targeted disruption of the myocilin gene do not express a phenotype. Experimental data indicate that mutated myocilin is not secreted and accumulates in cells which might critically impair the function of the TM.

Animals↗
PubMed2001

The role of myocilin/TIGR in glaucoma: results of the Glaucoma Research Foundation catalyst meeting in Berkeley, California, March 2000.

Approximately 3 years ago, the first major (biochemical, molecular biologic, and biologic) insight into primary open-angle glaucoma was the finding that mutations in the myocilin (MYOC/TIGR) gene were related to certain forms of juvenile onset of this disease. Since then, a great deal of work has been done to determine the possible mechanisms by which MYOC/TIGR might cause not only juvenile but also adult-onset primary open-angle glaucoma. To assess the current knowledge and those areas in which more research is necessary, a meeting of scientists was held by the Glaucoma Research Foundation of San Francisco, California in the spring of 2000. This meeting attempted to concentrate on the MYOC/TIGR protein rather than the genetics of this gene. Possible functions and roles of this protein intracellularly and extracellularly were critically examined and discussed. Normal transcriptional and translational events and the effect of mutations on these events were explored. The discussions yielded insight not only in those areas in which important information is known but also in vital areas in which little is currently understood. This review attempts to summarize the current knowledge regarding MYOC/TIGR and to elucidate the points that the people attending the meeting thought needed further study.

Cytoskeletal Proteins↗
PubMed2001

The presence and properties of myocilin in the aqueous humor.

PURPOSE: To determine whether myocilin is present in the aqueous humor (AH) and to examine certain properties of this protein. METHODS: Human AH was obtained at the time of either glaucoma surgery or cataract extraction. Monkey AH was obtained at the time of death, and bovine aqueous was obtained from eyes delivered from an abattoir. Column chromatography was performed on aqueous samples to determine the approximate size of the myocilin present. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blot analysis were performed using antibody prepared against a peptide sequence in myocilin. Analysis of the bovine proteins present in AH that were retained by a microporous filter was also performed using western blot analysis. RESULTS: By western blot analysis, myocilin was present in human, monkey, and bovine AH. The apparent molecular size of the myocilin present in the AH were greater than 250,000 Da, when quantified with a gel filtration column. Myocilin appeared to be hydrophobic and was one of the proteins that was retained on microporous filters that were obstructed by AH. CONCLUSIONS: Myocilin is a constituent in the AH. It appears that myocilin is a hydrophobic protein that may exist in an oligomeric state or in association with other proteins. Myocilin is retained by microporous filters and may be involved in the obstruction of these filters that occurs when AH is perfused through them.

Animals↗
PubMed2001

Expression of cyclooxygenase-1 and -2 in normal and glaucomatous human eyes.

PURPOSE: Primary open-angle glaucoma (POAG) is the predominant form of chronic glaucoma, but the underlying pathologic mechanisms are largely unknown. Because prostaglandins (PGs) have been introduced into POAG treatment with remarkable success, this study was undertaken to investigate whether a change in the expression of the PG-synthesizing enzymes cyclooxygenase (COX)-1 and -2 might be involved in the pathogenesis of POAG. METHODS: Expression of COX-1 and -2 was assessed by confocal laser microscopy, immunohistochemistry, Western blot analysis, and real-time RT-PCR in human eyes with different forms of glaucoma (primary open-angle, angle-closure, congenital juvenile, and steroid-induced), as well as in age-matched control eyes. Additionally, PGE2 was measured in aqueous humor by means of an enzyme-linked immunoassay as a product of COX activity. RESULTS: In normal eyes, ocular COX-1 and -2 expression were largely confined to the nonpigmented secretory epithelium of the ciliary body. By immunohistochemistry and real-time RT-PCR, COX-2 expression was completely lost in the nonpigmented secretory epithelium of the ciliary body of eyes with end-stage POAG, whereas COX-1 expression was unchanged. By immunohistochemistry, in the ciliary bodies of eyes in five patients with diagnosis of early POAG, eyes in two had complete loss of COX-2 expression and in three showed only a few remaining scattered COX-2-expressing cells. COX-2 expression in the ciliary body was also lost in patients with steroid-induced glaucoma and was reduced in patients receiving topical steroid treatment. Eyes of patients with either congenital juvenile or angle-closure glaucoma showed COX-2 expression indistinguishable from control eyes. Aqueous humor of eyes with POAG contained significantly less PGE2 than control eyes. CONCLUSIONS: Both cyclooxygenase isoforms are constitutively expressed in the normal human eye. Specific loss of COX-2 expression in the nonpigmented secretory epithelium of the ciliary body appears to be linked to the occurrence of POAG and steroid-induced glaucoma.

Adult↗
PubMed2001

AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach.

PURPOSE: To study the role of alphaB-crystallin (alphaB) in the developing lens and its importance in lens structure and function. METHODS: Gene targeting in embryonic stem cells was used to generate mouse lines in which the alphaB gene and its protein product were absent. Gene structure and expression were characterized by genomic Southern blot, immunoblot, and Northern blot analyses, and two-dimensional gel electrophoresis. The gene knockout mice were screened for cataract with slit lamp biomicroscopy, and dissected lenses were examined with dark-field microscopy. Lenses and other tissues were analyzed by standard histology and immunohistochemistry. Chaperone activity was determined by heating lens homogenate supernatants and measuring absorbance changes. RESULTS: In an unexpected result, lenses in the alphaB gene knockout mice developed normally and were remarkably similar to wild-type mouse lenses. All the other crystallins were present. The thermal stability of a lens homogenate supernatant was mildly compromised, and when oxidatively stressed in vivo with hyperbaric oxygen, the knockout lenses reacted similarly to wild type. In targeting the alphaB gene, the adjacent HSPB2 gene, which is not expressed in the lens, was also disrupted. Loss of alphaB and/or HSPB2 function leads to degeneration of some skeletal muscles. CONCLUSIONS: AlphaB is not essential for normal development of a transparent lens in the mouse, and therefore is more dispensable to the lens than the closely related alphaA-crystallin. It may play a small role in maintaining transparency throughout life. alphaB and/or the closely related HSPB2 is required to maintain muscle cell integrity in some skeletal muscles.

Aging↗
PubMed2000

Omega -crystallin of the scallop lens. A dimeric aldehyde dehydrogenase class 1/2 enzyme-crystallin.

While many of the diverse crystallins of the transparent lens of vertebrates are related or identical to metabolic enzymes, much less is known about the lens crystallins of invertebrates. Here we investigate the complex eye of scallops. Electron microscopic inspection revealed that the anterior, single layered corneal epithelium overlying the cellular lens contains a regular array of microvilli that we propose might contribute to its optical properties. The sole crystallin of the scallop eye lens was found to be homologous to Omega-crystallin, a minor crystallin in cephalopods related to aldehyde dehydrogenase (ALDH) class 1/2. Scallop Omega-crystallin (officially designated ALDH1A9) is 55-56% identical to its cephalopod homologues, while it is 67 and 64% identical to human ALDH 2 and 1, respectively, and 61% identical to retinaldehyde dehydrogenase/eta-crystallin of elephant shrews. Like other enzyme-crystallins, scallop Omega-crystallin appears to be present in low amounts in non-ocular tissues. Within the scallop eye, immunofluorescence tests indicated that Omega-crystallin expression is confined to the lens and cornea. Although it has conserved the critical residues required for activity in other ALDHs and appears by homology modeling to have a structure very similar to human ALDH2, scallop Omega-crystallin was enzymatically inactive with diverse substrates and did not bind NAD or NADP. In contrast to mammalian ALDH1 and -2 and other cephalopod Omega-crystallins, which are tetrameric proteins, scallop Omega-crystallin is a dimeric protein. Thus, ALDH is the most diverse lens enzyme-crystallin identified so far, having been used as a lens crystallin in at least two classes of molluscs as well as elephant shrews.

Aldehyde Dehydrogenase↗
PubMed2000

Regulation of human myocilin/TIGR gene transcription in trabecular meshwork cells and astrocytes: role of upstream stimulatory factor.

BACKGROUND: Mutations in the myocilin (MYOC)/TIGR gene are responsible for autosomal-dominant juvenile primary open-angle glaucoma (POAG). In patients with non-autosomal-dominant POAG, such mutations are rare, but the expression of MYOC/TIGR in the trabecular meshwork (TM) of the eye is considerably higher than in normals. We performed transfection, DNAse I footprinting, mutagenesis and electrophoretic mobility shift assays (EMSA) to identify elements responsible for the basal transcription of MYOC/TIGR in TM cells and astrocytes. RESULTS: DNAse I footprinting experiments of the human MYOC/TIGR promoter showed a major protected area between nt -106 to -77, which was not conserved in the homologous region of the mouse myoc/tigr promoter. In addition, the TATA-box was protected, as well as at least three downstream sites, including an AP-1-like sequence. Deletion of the -106 to -77 region caused a substantial loss of functional promotor activity in all cell types. Site-directed mutagenesis and EMSA experiments revealed the presence of two regulatory elements in the -106 to -77 region. Each of these cis-elements is essential for minimal promoter activity. The 5'-half of the region contains a sequence with similarities to NF-kappaB-related sites, however, binding of NF-kappaB could not be confirmed by EMSA. The 3'-half contains a canonical E-box sequence. EMSA experiments showed that the upstream regulatory factor (USF) was binding to the E-box sequence and that the binding can be supershifted by specific antibodies. CONCLUSIONS: Several DNA-protein binding elements contribute to a transcription of MYOC/TIGR, and USF is critically required for its basal transcription in trabecular meshwork cells and astrocytes.

Animals↗
PubMed2000

Localization of myocilin/trabecular meshwork--inducible glucocorticoid response protein in the human eye.

PURPOSE: To study distribution and cellular localization of myocilin/trabecular meshwork-inducible glucocorticoid response protein (TIGR) in the human eye. METHODS: A peptide antibody against a portion of the myosin-like domain of myocilin/TIGR was developed. Different ocular tissues from three human donors were investigated by one- and two-dimensional gel electrophoresis and Western blot analysis. Immunohistochemistry was performed on 25 human eyes enucleated because of posterior choroidal melanoma and on 7 normal human donor eyes. RESULTS: By Western blot analysis, a band at approximately 57 kDa was visualized in cornea, trabecular meshwork, lamina cribrosa, optic nerve, retina, iris, ciliary body, and vitreous humor. By immunohistochemistry, immunoreactivity for myocilin/TIGR was observed in cells of the corneal epi- and endothelium and extracellularly in the corneal stroma and sclera. In the trabecular meshwork, cells of the uveal and corneoscleral meshwork were stained, as was the cribriform area directly adjacent to Schlemm's canal. Positive staining was seen in cells of the ciliary epithelium, ciliary muscle, lens epithelium, and in stromal and smooth muscle cells of the iris. Throughout the entire vitreous body, fine filamentous material was positively labeled. In the retina, staining was seen along the outer surface of rods and cones, in neurons of the inner and outer nuclear layer, and in the axons of optic nerve ganglion cells. Optic nerve axons were stained in the prelaminar, laminar, and postlaminar parts of the nerve. In the region of the lamina cribrosa, astrocytes in the glial columns and cribriform plates were positively labeled. CONCLUSIONS: Myocilin TIGR is expressed in almost every ocular tissue. Depending on the respective tissue, it is observed extra- or intracellularly. The presence of myocilin/TIGR in optic nerve axons and lamina cribrosa astrocytes indicates that the trabecular meshwork might not be the only target of abnormal myocilin/TIGR in GLC1A-linked open-angle glaucoma.

Aged↗
PubMed1999

Development of characterization of a immortal and differentiated murine trabecular meshwork cell line.

PURPOSE: To study mouse trabecular meshwork (TM) and to develop a murine TM cell line. METHODS: Mouse TM in situ was studied by light and electron microscopy (EM). In addition, TM was isolated from the H-2K(b)-tsA58 transgenic mouse strain in which promoter sequences of the major histocompatibility complex H-2Kb class 1 gene are fused to sequences of the SV40 mutant temperature-sensitive (ts) strain tsA58. The promoter is inducible by interferon (IFN)-gamma, and the tsA58 gene product is active at 33 degrees C (permissive conditions), but not at 37 degrees C (nonpermissive conditions). The TM explant was cultured in permissive conditions. Outgrowing cells were passaged through two rounds of single-cell cloning. One clonal cell line (MUTM-NEI/1) was characterized in nonpermissive conditions by EM, immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR), and northern blot hybridization. In addition, MUTM-NEI/1 cells were transfected with plasmid DNA. RESULTS: The mouse eye has a circumferentially oriented outflow vessel and a TM that is subdivided in an outer juxtacanalicular or cribriform part and an inner lamellated or trabecular part. From the TM of the H-2Kb-tsA58 mouse, a clonal cell line (MUTM-NEI/1) was established. In permissive conditions, MUTM-NEI/1 cells remained proliferative through at least 80 generations without change in phenotype. In nonpermissive conditions, proliferation was slower, and MUTM-NEI/1 cells differentiated and synthesized collagen types I, III, IV, and VI; laminin; and fibronectin. MUTM-NEI/1 cells were immunoreactive for vimentin, alphaB-crystallin, and neural cell adhesion molecule (NCAM), but not for desmin or cytokeratin. Less than 10% of MUTM-NEI/1 cells stained for alpha-smooth muscle actin, whereas after 3 days of treatment with transforming growth factor-beta1 almost all cells were positive. MUTM-NEI/1 cells expressed mRNA for NCAM, aquaporin 1, myocilin/trabecular meshwork glucocorticoid-inducible protein, and alphaB-crystallin, which was increased after oxidative stress. MUTM-NEI/1 cells could be successfully transfected with plasmid DNA. CONCLUSIONS: The architecture of the murine outflow system is comparable to that in primates. The MUTM-NEI/1 cell line is a clonal, immortal, and differentiated TM cell line that will be an important tool for study of the expression of TM genes.

Animals↗
PubMed1999

Modulation of myocilin/TIGR expression in human trabecular meshwork.

PURPOSE: To study factors that modulate myocilin/trabecular meshwork inducible glucocorticoid response protein (TIGR) mRNA expression in human trabecular meshwork (TM). METHODS: mRNA from fresh TM of four human donors, from perfused anterior segment organ cultured TM of three donors, and from four primary TM cell lines of different donors was isolated. The full length cDNA of myocilin/TIGR was cloned from TM mRNA using a polymerase chain reaction approach and used as probe for northern blot analysis hybridization. Trabecular meshwork cell cultures were treated with transforming growth factor (TGF)-beta1 (1 ng/ml), dexamethasone (10(-7) M), and mechanical stretch (10%). RESULTS: mRNA for myocilin/TIGR could be readily detected by northern blot analysis hybridization in 2 to 3 microg of total RNA from all fresh and all organ-cultured TM samples. In contrast, no mRNA for myocilin/TIGR could be detected in 20 microg of total RNA isolated from three different primary TM cell lines. Only one TM cell line had a baseline expression of myocilin/TIGR, which was 35- to 55-fold lower than that of fresh or organ-cultured TM samples. Treatment of TM cell cultures with dexamethasone for 1 day markedly increased expression of myocilin/TIGR mRNA, an effect that was even more pronounced after 3 days of treatment. Treatment with TGF-beta1 for 24 hours had no effect; however, after 3 and 12 days of treatment a 3.8- and 4-fold increase in myocilin/TIGR mRNA expression was observed. Expression of myocilin/TIGR mRNA was also increased after 10% mechanical stretch; however, in contrast to the effects of TGF-beta-1, this effect was observed much earlier (8-24 hours) after treatment. CONCLUSIONS: Dynamic mechanical stimuli maintain myocilin/TIGR expression in TM in situ and lack of these stimuli in monolayer cell cultures might be involved in downregulation of myocilin/TIGR expression.

Adult↗
PubMed1998

Characterization of the mouse Myoc/Tigr gene.

Mutations in the myocilin (MYOC), also known as Trabecular meshwork-Inducible Glucocorticoid Response (TIGR) gene can lead to juvenile open-angle glaucoma in human and may be responsible for at least 3% of primary open-angle glaucoma. To develop a mouse model of primary open angle glaucoma, and to get deeper insight into the mechanisms of the MYOC/TIGR gene regulation and function, we have isolated and characterized full size mouse Myoc/Tigr cDNA and genomic clones. The mouse and human MYOC/TIGR genes have the same exon-intron structure and contain 3 exons, although the mouse gene is 6 kb shorter than the human gene (10 kb versus 16 kb) due to differences in the length of introns. The MYOC/TIGR gene encodes a moderately conserved protein, which is 82% identical between human and mouse. The encoded protein is 14 amino acids shorter at the N-terminus in the mouse than in the human (490 versus 504 amino acids). Mouse and human MYOC/TIGR genes show a similar pattern of expression in adult ocular and nonocular tissues. The mouse Myoc/Tigr gene was mapped to Chromosome 1 at position 82.8 cM from the centromere. All residues, which were identified in the human MYOC/TIGR protein as critical for glaucoma development, are conserved in the mouse Myoc/Tigr.

Adult↗
PubMed1998

Effects of transforming growth factor-beta1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma.

The influence of transforming growth factor-beta1 (TGF-beta1) and basic fibroblast growth factor (bFGF) on growth of cell cultures derived from unilateral vestibular nerve schwannomas was investigated. Cell cultures were initiated from 9 schwannomas and characterized immunocytochemically with antibodies against S-100 and type IV collagen. The effects of TGF-beta1 and bFGF on DNA synthesis in chemically defined serum-free medium were assessed by measuring the incorporation of 5-bromo-2'-deoxy-uridine (BRDU) into cellular DNA. Cell proliferation was evaluated with an electronic cell counter. Reverse transcription polymerase chain reaction (RT-PCR) was performed using oligonucleotide primers specific for TGF-beta1 and TGF-beta2. TGF-beta1 stimulated DNA synthesis in a dose dependent manner. Maximal stimulation was observed at a concentration of 1 ng/ml, which induced a nearly 2-fold increase in DNA content. This effect was not seen when TGF-beta1 was added in the presence of neutralizing antibodies. In addition, antibodies against TGF-beta1 significantly reduced DNA synthesis in control cultures without supplemented exogenous growth factors. bFGF alone had no significant effects on DNA synthesis. In contrast, when TGF-beta1 and bFGF were added together, the mitogenic response was much greater than produced by TGF-beta1 alone. RT-PCR showed that the cultured cells expressed mRNA for both TGF-beta1 and TGF-beta2. We hypothesize that TGF-beta1 is an autocrine growth factor for human vestibular nerve schwannomas in culture. A similar mechanism might be involved in the growth of these tumors in situ.

Adult↗
PubMed1997

Superior cervical ganglionectomy in monkeys: light and electron microscopy of the anterior eye segment.

Morphological changes in the anterior eye segment of eight cynomolgus monkeys were investigated 2 days to 2.2 years after unilateral surgical superior cervical ganglionectomy (SCGx). SCGx was confirmed by histologic examination of the excised surgical specimen and persistent ipsilateral miosis. In four short-term monkeys (2, 4, 7 and 11 days), iris, ciliary muscle and trabecular meshwork were studied by electron microscopy. In the other four longer-term monkeys (3 week, 4 week, 5 week, 2.2 year) the anterior eye segment was investigated with tyrosine hydroxylase immunohistochemistry (TH-IR) and catecholamine fluorescence (CF). Electron microscopy of experimental eyes showed characteristic signs of Wallerian degeneration in numerous nerve fibers and terminals in the iris, but to a lesser extent in the ciliary muscle and the trabecular meshwork. TH-IR and CF showed marked interindividual differences. In all experimental eyes, there was a marked reduction, but never a complete absence of adrenergic nerves in the iris. In two animals (4 week and 2.2 years), the adrenergic innervation of the ciliary body and the chamber angle was similarly reduced. In contrast, in the experimental eyes of the other two animals (3 and 5 weeks), changes in adrenergic innervation to the ciliary body and chamber angle were minimal or absent. The results indicate that following apparently complete SCGx in the cynomolgus monkey, reduction of adrenergic innervation to the iris as evidenced by pupillary physiology, electron microscopy, TH-IR and CF does not guarantee reduction in adrenergic innervation to the ciliary body and trabecular meshwork. SCGx may not extirpate all third order sympathetic neurons in the distal stump, or there may be a significant contribution of accessory ganglion cells to the adrenergic innervation of the anterior eye segment.

Adrenergic Fibers↗
PubMed1997

Nitrergic nerve cells in the primate ciliary muscle are only present in species with a fovea centralis.

Nerve cells positive for NADPH diaphorase (D)/nitric oxide synthase in the human ciliary muscle appear to be involved in relaxation of the muscle during disaccommodation. To study whether similar cells might mediate disaccommodation of the primate ciliary muscle in general, serial sections of the ciliary muscle of 5 cynomolgus monkeys (Macaca fascicularis) and 2 owl monkeys (Aotes trivirgatus) were stained for NADPH-D. Both monkey species have a ciliary muscle system and an accommodative amplitude comparable to that in humans. Positively stained cells were frequently observed in the ciliary muscle of all cynomolgus monkeys, a diurnal species with a fovea, but never in owl monkeys, a nocturnal species without a fovea. The results indicate that NADPH-D-positive and probably nitrergic ganglion cells in the ciliary muscle are not present in all primate species, but only in those with high requirements for visual acuity. They might smoothen the ciliary-ganglion-mediated contraction of the ciliary muscle or contribute to the small fluctuations or oscillations of accommodation that are observed under steady viewing conditions.

Accommodation, Ocular↗
PubMed1996

Ciliary body.

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Cell Communication↗
PubMed1996

Transforming growth factor-beta 1 induces alpha-smooth muscle-actin expression in cultured human and monkey trabecular meshwork.

Transforming growth factor-beta 1 (TGF-beta 1) induces alpha-smooth muscle (sm)-actin expression and a contractile myofibroblast-like phenotype in a considerable number of different cell types. Since alpha-sm-actin is expressed in some of the resident human trabecular meshwork (TM) cells in situ, and TGF-beta 1 is synthesized by TM in vitro, alpha-sm-actin expression in TM might also be under the influence of TGF-beta 1. To assess this question, TM cultures were initiated from the eyes of three human donors and three cynomolgus monkeys. Various doses of TGF-beta 1 (0.5-5 ng ml-1) were added to confluent cultures from third to fourth passages. Experiments were performed in the presence of fetal calf serum or under chemically defined serum-free conditions. Four days after treatment, cells were stained immunocytochemically for alpha-sm-actin, and the number of positively labelled cells was quantitatively evaluated. In addition, reverse transcription polymerase chain reaction (PCR) was performed using oligonucleotide primers specific for alpha-sm-actin. In control cultures supplemented with serum, 19.0 +/- 9.4% of human meshwork cells, and 10.2 +/- 4.5% of monkey meshwork cells expressed immunoreactivity for alpha-sm-actin. In human cultures, this number was significantly higher in serum-free conditions (34.1 +/- 7.7%). Treatment with TGF-beta 1 induced alpha-sm-actin expression in a dose-dependent manner. At 5 ng ml-1 TGF-beta 1, 75.5 +/- 7.1% of human meshwork cells expressed distinct stress fibers that stained positively for alpha-sm-actin (P < or = 0.01). A similar albeit smaller increase in alpha-sm-actin positive cells was observed in monkey cultures following treatment with TGF-beta 1. These effects were seen with and without serum, but not when TGF-beta 1 was supplemented in the presence of neutralizing antibodies. In PCR experiments, a distinct product was amplified with cDNA derived from cells treated with 0.1 ng and 1 ng ml-1 TGF-beta 1, but not in control cultures. We conclude that TGF-beta 1 may play a role in differentiating TM cells towards a myofibroblast-like cell type by modulating the expression of alpha-sm-actin.

Actins↗