A recent study with bone marrow chimera mice suggested that, bleomycin induces inflammation and fibrosis in wild type through TNF synthesis that triggers TGF-β release; TGF-β promotes fibroblasts deposition and regulates TNF synthesis from macrophages.
B: In WT>SPARC KO chimeras, despite a normal parenchyma inflammation, collagen deposition by fibroblasts is greatly reduced and results in milder fibrosis.
C: In SPARC KO>WT chimeras, the inability of SPARC KO macrophages to down-modulate TNF production in response to TGF-β results in exaggerated and persistent inflammation and severe fibrosis.
Reference
Am J Pathol. 2011 Oct 11. [Epub ahead of print]
SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage.
Sangaletti S, Tripodo C, Cappetti B, Casalini P, Chiodoni C, Piconese S, Santangelo A, Parenza M, Arioli I, Miotti S, Colombo MP.
Source
Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sparc(-/-) macrophages to down-regulate tumor necrosis factor production because of impaired responses to tumor growth factor-β. Hence, the use of bone marrow cells expressing a dominant-negative form of tumor growth factor-β receptor type II under the monocyte-specific CD68 promoter, as a decoy, phenocopied Sparc(-/-) donor chimeras. Our results point to an unexpected dual role of SPARC in oppositely influencing the outcome of fibrosis.
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID: 22001347 [PubMed - as supplied by publisher]
B: In WT>SPARC KO chimeras, despite a normal parenchyma inflammation, collagen deposition by fibroblasts is greatly reduced and results in milder fibrosis.
C: In SPARC KO>WT chimeras, the inability of SPARC KO macrophages to down-modulate TNF production in response to TGF-β results in exaggerated and persistent inflammation and severe fibrosis.
Reference
Am J Pathol. 2011 Oct 11. [Epub ahead of print]
SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage.
Sangaletti S, Tripodo C, Cappetti B, Casalini P, Chiodoni C, Piconese S, Santangelo A, Parenza M, Arioli I, Miotti S, Colombo MP.
Source
Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Abstract
Fibrosis results from inflammatory tissue damage and impaired regeneration. In the context of bleomycin-induced pulmonary fibrosis, we demonstrated that the matricellular protein termed secreted protein acidic and rich in cysteine (SPARC) distinctly regulates inflammation and collagen deposition, depending on its cellular origin. Reciprocal Sparc(-/-) and wild-type (WT) bone marrow chimeras revealed that SPARC expression in host fibroblasts is required and sufficient to induce collagen fibrosis in a proper inflammatory environment. Accordingly, Sparc(-/-) WT chimeras showed exacerbated inflammation and fibrosis due to the inability of Sparc(-/-) macrophages to down-regulate tumor necrosis factor production because of impaired responses to tumor growth factor-β. Hence, the use of bone marrow cells expressing a dominant-negative form of tumor growth factor-β receptor type II under the monocyte-specific CD68 promoter, as a decoy, phenocopied Sparc(-/-) donor chimeras. Our results point to an unexpected dual role of SPARC in oppositely influencing the outcome of fibrosis.
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
PMID: 22001347 [PubMed - as supplied by publisher]
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