SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage

Sangaletti, Sabina; Tripodo, Claudio; Cappetti, Barbara; Casalini, Patrizia; Chiodoni, Claudia; Piconese, Silvia; Santangelo, A; Parenza, Mariella; Arioli, Ivano; Miotti, Silvia; Colombo, Mario P.

doi:10.1016/j.ajpath.2011.08.027

Cited by 66 publications

(91 citation statements)

References 53 publications

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“…2A ). In contrast, defective collagen remodeling was expected in Sparcdefi cient mice in response to stress ( 15,16 ), similar to what occurs in Fas -defi cient lpr/lpr/Sparc −/− mice, where the need to accommodate the exacerbated proliferation of CD3 + B220 + double positive T cells is not supported by proper collagen rearrangement (Supplementary Fig. S2B).…”

Section: Exacerbated Autoimmunity and Lymphoproliferation In Fas -Mutmentioning

confidence: 65%

“…Moreover, the higher rate of NETosis in lpr/lpr/Sparc −/− mice compared with lpr/lpr/ Sparc +/+ mice underscores the role of SPARC in ECM organization, neutrophil activation, and NETosis. These events could result from the exacerbated infl ammation observed in response to SPARC defi ciency ( 16 ), together with the uncontrolled induction of NETosis due to defective ECM inhibition. Considering the tight association between SLE, NETosis, and the activation of IFN pathways ( 35,36 ), we investigated the gene expression profi le (GEP) of neutrophils isolated ex vivo from lpr/lpr/Sparc +/+ and lpr/lpr/Sparc −/− spleens.…”

Section: Increased Netosis In Lpr/lpr/sparc -/-Mice Depends On Reducementioning

confidence: 99%

“…Cell lysate preparation and Western blot analysis were carried out as previously described ( 16 ). The following antibodies were used for immunoreactions: polyclonal rabbit anti-SYK, anti-p-ZAP70/SYK, and anti-IκBα/p-IκBα (Cell Signaling Technology) and anti-actin (Sigma).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…15 ). SPARC is a nonstructural pleiotropic matricellular protein that is a key regulator of tissue stroma remodeling in physiologic conditions and pathologic settings, including cancer and parenchymal fi brosis ( 16 ). SPARC also plays a role in the profound changes that occur in the tissue architecture of solid and hematologic neoplasms ( 17,18 ).…”

Section: Introductionmentioning

confidence: 99%

“…SPARC also plays a role in the profound changes that occur in the tissue architecture of solid and hematologic neoplasms ( 17,18 ). SPARC produced by innate immune cells infl uences the cross-talk between cancer cells and the ECM at the invasive edge of primary tumors and regulates proinfl ammatory TNF production in response to tissue damage ( 16 ). Moreover, bone marrow stroma-derived SPARC was reported to regulate the expansion of myeloid cell populations under myeloproliferative stress ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Defective Stromal Remodeling and Neutrophil Extracellular Traps in Lymphoid Tissues Favor the Transition from Autoimmunity to Lymphoma

et al. 2014

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Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5 + B cells, which underwent malignant transformation due to defective apoptosis under the pressure of neutrophil-derived trophic factors and NF-κB activation. Furthermore, this model of defective stromal remodeling during lymphomagenesis correlates with human lymphomas arising in a SPARC-defective environment, which is prototypical of CD5 + B-cell chronic lymphocytic leukemia (CLL). SIGNIFICANCE:These results reveal the importance of stromal remodeling in SLO to accommodate autoimmune lymphoproliferation while preventing lymphomagenesis. Our fi ndings reveal a link between SPARC, collagen deposition, and the engagement of the immune-inhibitory receptor LAIR-1 on neutrophils, neutrophil cell death via NETosis, and the stimulation of CD5 + B-cell proliferation. Moreover, we show that SPARC defi ciency promotes CD5 + B-cell lymphomagenesis and is correlated with CLL in humans. Cancer Discov; 4(1);

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Section: Exacerbated Autoimmunity and Lymphoproliferation In Fas -Mutmentioning

confidence: 65%

Section: Increased Netosis In Lpr/lpr/sparc -/-Mice Depends On Reducementioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Defective Stromal Remodeling and Neutrophil Extracellular Traps in Lymphoid Tissues Favor the Transition from Autoimmunity to Lymphoma

et al. 2014

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SPARC acts as a mediator of TGF‐β1 in promoting epithelial‐to‐mesenchymal transition in A549 and H1299 lung cancer cells

et al. 2018

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Migration and metastasis of tumor cells greatly contributes to the failure of cancer treatment. Recently, the extracellular protein secreted protein acidic and rich in cysteine (SPARC) has been reported closely related to tumorigenesis. Some articles have suggested that SPARC promoted metastasis in several highly metastatic tumors. However, there are also some studies shown that SPARC acted as an antitumor factor. SPARC-induced epithelial-tomesenchymal transition (EMT) in melanoma cells and promoted EMT in hepatocellular carcinoma. Therefore, the role of SPARC in tumorigenesis and its relationship with EMT is still unclear. In this study, we investigated the expression change of SPARC in A549 and H1299 lung cancer cells undergoing EMT process. Our study indicated that SPARC was upregulated in A549 and H1299 cells EMT process. We further investigated the function of SPARC on proliferation, migration, and EMT process of A549 and H1299 cells. Overexpression of SPARC promoted the migration and EMT of A549 and H1299 cells. Knockdown SPARC inhibited the EMT of A549 cells. Overexpression of SPARC induced the increased expression of p-Akt and P-ERK. Furthermore, exogenous SPARC peptide promoted transforming growth factor (TGF)-β1-induced EMT of A549 and H1299 cells. SPARC knockdown partially eliminated TGF-β1 function in inducing EMT of A549 cells. SPARC follistatin-like functional domain reduced the expression of E-cadherin, but had no effect on the expression of p-Akt and p-ERK. In conclusion, we elucidated that SPARC contributes to tumorigenesis by promoting migration and EMT of A549 and H1299 lung cancer cells. These results will provide some new suggestion for lung cancer treatment. © 2018 BioFactors, 44(5):453-464, 2018Abbreviations: A549, A human lung adenocarinoma epithelial cell line; Akt, A serine/threonine-specific protein kinase; BSA, bovine serum albumin; CCK-8, cell counting kit-8; DMEM, Dulbecco's modified Eagle's Medium; EC, extracellular calcium-binding domain; EDTA, ethylenediaminetetraacetic acid; EGFP, enhancer green fluorescent protein; EGF, epidermal growth factor; EMT, epithelial-to-mesenchymal transition; ERK, extracellular signal-regulated kinases; FBS, fetal bovine serum; FS, follistatin-like functional domain; Fyn, Fyn proto-oncogene, Src family tyrosine kinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; H1299, A human non-small cell lung carcinoma cell line; ILK, integrin-linked kinase; MDM2, mouse double minute 2 homolog; NF-κB, nuclear factor kappa B subunit 1; Nab-PTX, nanoparticle albumin bound paclitaxel; NSCLC, nonsmall cell lung cancer; NT, N terminal acidic domain; PBS, phosphate-buffered saline; PARP, poly (ADP-ribose) polymerase 1; PMSF, phenylmethane sulfonyl fluoride; RIPA, radioimmunoprecipitation assay buffer; SDS, sodium dodecyl sulfate; SPARC, secreted protein acidic and rich in cysteine; TGF-β, transforming growth factor; TBST, a mixture of tris-buffered saline and Tween 20 Additional Supporting Information may be found in the online version of this article.

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Comparative proteome profiling of bleomycin‐induced lung toxicity in rats by 2D–nano‐LC–MS/MS and spectral counting

Zhou

Sun

Jiang

2016

Biomedical Chromatography

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The mechanisms involved in bleomycin-induced lung toxicity have not been fully understood to date. This work aimed to compare the proteome profiling of bleomycin-induced lung toxicity by using 2D-nano-LC-MS/MS and spectral counting. By comparing the spectral counts of identified proteins between control and bleomycin-treated groups, we noted that 102 proteins were upregulated and 28 proteins were downregulated in the bleomycin-treated group. Among these differently expressed proteins, five proteins were chosen for validation by Western blot analysis. The levels of these five proteins were consistent with proteomic results. These potential mediators can facilitate the translation of the underlying mechanisms of bleomycin-induced lung toxicity to molecular targets in the clinical arena.

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SPARC Oppositely Regulates Inflammation and Fibrosis in Bleomycin-Induced Lung Damage

Cited by 66 publications

References 53 publications

Defective Stromal Remodeling and Neutrophil Extracellular Traps in Lymphoid Tissues Favor the Transition from Autoimmunity to Lymphoma

Defective Stromal Remodeling and Neutrophil Extracellular Traps in Lymphoid Tissues Favor the Transition from Autoimmunity to Lymphoma

SPARC acts as a mediator of TGF‐β1 in promoting epithelial‐to‐mesenchymal transition in A549 and H1299 lung cancer cells

Comparative proteome profiling of bleomycin‐induced lung toxicity in rats by 2D–nano‐LC–MS/MS and spectral counting

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