Persistent Transforming Growth Factor-Beta 1 Expression May Predict Peritoneal Fibrosis in CAPD Patients with Frequent Peritonitis Occurrence

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Abstract

The efficiency of continuous ambulatory peritoneal dialysis depends on the permeability of the peritoneal membrane. Peritoneal fibrosis (PF) causes loss of the dialytic function. Several studies have indicated that PF is closely related to the proliferation of peritoneal fibroblasts and the deposition of extracellular matrix. Transforming growth factor-beta 1 (TGF-β1) plays a major role in stimulating extracellular matrix deposition. Frequent peritonitis occurrence may cause persistent TGF-β1 mRNA expression. In an attempt to search for a factor related to PF, we designed a longitudinal study to measure TGF-β1 levels in dialysate and TGF-β1 mRNA expression in peritoneal mononuclear cells from peritoneal dialysate before onset, once a week during peritonitis, and after peritonitis in high and low peritonitis occurrence (HPO and LPO) patients. Fifteen patients with a LPO rate and 5 patients with a HPO rate were followed up longitudinally. Meanwhile, TGF-β1 levels and TGF-β1 mRNA expression were augmented in peritoneal dialysate effluents before, during, and after the episodes of peritonitis. The peritoneal permeability was evaluated by the peritoneal equilibration test. The results revealed that in the LPO group, TGF-β1 and TGF-β1 mRNA were detectable at early stages of peritonitis, but the levels decreased rapidly and were undetectable 2 weeks after peritonitis. On the other hand, in the HPO group, TGF-β1 and TGF-β1 mRNA persisted for a long time. We could detect TGF-β1 and TGF-β1 mRNA in dialysate effluents and peritoneal mononuclear cells even 2, 3, and 4 weeks after episodes of peritonitis. When compared with that of first or second episode of peritonitis, the peritoneal function evaluated with the peritoneal equilibration test was found to obviously deteriorate during the third episode of peritonitis. These findings were confirmed by an in situ hybridization technique to evaluate the relationship between TGF-β1 mRNA expression and PF from biopsied peritoneal specimens. These findings suggest that the high TGF-β1 levels in the dialysate are related to an increased expression of TGF-β1 in the peritoneum. Thus, the persistent TGF-β1 expression in the peritoneum may serve as a useful parameter in predicting PF in continuous ambulatory peritoneal dialysis patients with frequent peritonitis occurrence.

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Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth

MB Sporn, LM Wakefield, R Derynck … (1986)

This study examines the potential role of transforming growth factor beta (TGF-beta) in the regulation of human T lymphocyte proliferation, and proposes that TGF-beta is an important autoregulatory lymphokine that limits T lymphocyte clonal expansion, and that TGF-beta production by T lymphocytes is important in T cell interactions with other cell types. TGF-beta was shown to inhibit IL-2-dependent T cell proliferation. The addition of picograms amounts of TGF-beta to cultures of IL-2-stimulated human T lymphocytes suppressed DNA synthesis by 60-80%. A potential mechanism of this inhibition was found. TGF-beta inhibited IL-2-induced upregulation of the IL-2 and transferrin receptors. Specific high-affinity receptors for TGF-beta were found both on resting and activated T cells. Cellular activation was shown to result in a five- to sixfold increase in the number of TGF- beta receptors on a per cell basis, without a change in the affinity of the receptor. Finally, the observations that activated T cells produce TGF-beta mRNA and that TGF-beta biologic activity is present in supernatants conditioned by activated T cells is strong evidence that T cells themselves are a source of TGF-beta. Resting T cells were found to have low to undetectable levels of TGF-beta mRNA, while PHA activation resulted in a rapid increase in TGF-beta mRNA levels (within 2 h). Both T4 and T8 lymphocytes were found to make mRNA for TGF-beta upon activation. Using both a soft agar assay and a competitive binding assay, TGF-beta biologic activity was found in supernatants conditioned by T cells; T cell activation resulted in a 10-50-fold increase in TGF- beta production. Thus, TGF-beta may be an important antigen-nonspecific regulator of human T cell proliferation, and important in T cell interaction with other cell types whose cellular functions are modulated by TGF-beta.

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Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.

Michelle J. Harper, Erkki Ruoslahti, W Border … (1992)

The central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta.

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Fibrogenic cytokines: the role of immune mediators in the development of scar tissue.

E. Kovacs (1990)

A variety of diseases that are characterized by fibrosis share common features including the proliferation of fibroblasts and the deposition of extracellular matrix. Fibrosis often begins as an inflammatory reaction with leukocyte infiltration followed by the elaboration of cytokines. Here, Elizabeth J. Kovacs argues that the aberrant production of these mediators sustains the connective tissue accumulation that results in permanent alteration in tissue structure and function.

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Author and article information

Journal

Journal ID (publisher-id): AJN

Journal ID (nlm-ta): Am J Nephrol

Journal ID (doi): 10.1159/issn.0250-8095

Title: American Journal of Nephrology

Publisher: S. Karger AG

ISSN (Print): 0250-8095

ISSN (Electronic): 1421-9670

Publication date Subscription-year: 1998

Publication date (Print): December 1998

Publication date (Electronic): 09 December 1998

Volume: 18

Issue: 6

Pages: 513-519

Affiliations

Departments of ^a Pediatrics and ^b Internal Medicine, Nephrology Section, Veterans General Hospital, ^c Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, ROC

Article

Publisher ID: 13397 Other ID: Am J Nephrol 1998;18:513–519

DOI: 10.1159/000013397

PubMed ID: 9845827

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