TY - JOUR
T1 - SPARC oppositely regulates inflammation and fibrosis in bleomycin-induced lung damage
AU - Sangaletti, Sabina
AU - Tripodo, Claudio
AU - Cappetti, Barbara
AU - Casalini, Patrizia
AU - Chiodoni, Claudia
AU - Piconese, Silvia
AU - Santangelo, Alessandra
AU - Parenza, Mariella
AU - Arioli, Ivano
AU - Miotti, Silvia
AU - Colombo, Mario P.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2011.08.027
DO - 10.1016/j.ajpath.2011.08.027
M3 - Article
C2 - 22001347
AN - SCOPUS:81255214580
VL - 179
SP - 3000
EP - 3010
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 6
ER -