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Fibrogenesis & Tissue Repair
Published in: Fibrogenesis & Tissue Repair 1/2016

Open Access 01-12-2016 | Research

Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis

Authors: Robert M. DiFazio, Joshua T. Mattila, Edwin C. Klein, Lauren R. Cirrincione, Mondraya Howard, Eileen A. Wong, JoAnne L. Flynn

Published in: Fibrogenesis & Tissue Repair | Issue 1/2016

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Abstract

Background

Tuberculosis (TB) chemotherapy clears bacterial burden in the lungs of patients and allows the tuberculous lesions to heal through a fibrotic process. The healing process leaves pulmonary scar tissue that can impair lung function. The goal of this study was to identify fibrotic mediators as a stepping-stone to begin exploring mechanisms of tissue repair in TB.

Methods

Hematoxylin and eosin staining and Masson’s trichrome stain were utilized to determine levels of collagenization in tuberculous granulomas from non-human primates. Immunohistochemistry was then employed to further interrogate these granulomas for markers associated with fibrogenesis, including transforming growth factor-β (TGFβ), α-smooth muscle actin (αSMA), phosphorylated SMAD-2/3, and CD163. These markers were compared across states of drug treatment using one-way ANOVA, and Pearson’s test was used to determine the association of these markers with one another.

Results

TGFβ and αSMA were present in granulomas from primates with active TB disease. These molecules were reduced in abundance after TB chemotherapy. Phosphorylated SMAD-2/3, a signaling intermediate of TGFβ, was observed in greater amounts after 1 month of drug treatment than in active disease, suggesting that this particular pathway is blocked in active disease. Collagen production during tissue repair is strongly associated with TGFβ in this model, but not with CD163+ macrophages.

Conclusions

Tissue repair and fibrosis in TB that occurs during drug treatment is associated with active TGFβ that is produced during active disease. Further work will identify mechanisms of fibrosis and work towards mitigating lung impairment with treatments that target those mechanisms.
Appendix
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Metadata
Title
Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis
Authors
Robert M. DiFazio
Joshua T. Mattila
Edwin C. Klein
Lauren R. Cirrincione
Mondraya Howard
Eileen A. Wong
JoAnne L. Flynn
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Fibrogenesis & Tissue Repair / Issue 1/2016
Electronic ISSN: 1755-1536
DOI
https://doi.org/10.1186/s13069-016-0043-3

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