Discordance in cathepsin B and cystatin C expressions in bronchoalveolar fluids between murine bleomycin-induced fibrosis and human idiopathic fibrosis

Kasabova, Mariana; Villeret, Bérengère; Gombault, Aurélie; Lecaille, Fabien; Reinheckel, Thomas; Marchand-Adam, S.; Couillin, Isabelle; Lalmanach, Gilles

doi:10.1186/s12931-016-0432-6

Cited by 12 publications

(9 citation statements)

References 19 publications

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“…These findings have potential implications in COPD 35,36 and pulmonary fibrosis. 37,38 In addition, several proteases related to angiogenesis were downregulated including EGF-like protein 7 (EGFL7), chordin like 1 (CHRDL1), C-type lectin domain containing 14A (CLEC14A), plexin domain containing 2 (PLXDC2), MMP9, and CTSL, which is consistent with the results indicating repressed angiogenesis in the COVID-19 lungs (Fig. 2).…”

Section: Interaction Network Reveals the Imbalance Of Biological Procsupporting

confidence: 88%

Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples

Leng

Cao²,

et al. 2020

Sig Transduct Target Ther

167

131

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The COVID-19 pandemic has emerged as a global health emergency due to its association with severe pneumonia and relative high mortality. However, the molecular characteristics and pathological features underlying COVID-19 pneumonia remain largely unknown. To characterize molecular mechanisms underlying COVID-19 pathogenesis in the lung tissue using a proteomic approach, fresh lung tissues were obtained from newly deceased patients with COVID-19 pneumonia. After virus inactivation, a quantitative proteomic approach combined with bioinformatics analysis was used to detect proteomic changes in the SARS-CoV-2-infected lung tissues. We identified significant differentially expressed proteins involved in a variety of fundamental biological processes including cellular metabolism, blood coagulation, immune response, angiogenesis, and cell microenvironment regulation. Several inflammatory factors were upregulated, which was possibly caused by the activation of NF-κB signaling. Extensive dysregulation of the lung proteome in response to SARS-CoV-2 infection was discovered. Our results systematically outlined the molecular pathological features in terms of the lung response to SARS-CoV-2 infection, and provided the scientific basis for the therapeutic target that is urgently needed to control the COVID-19 pandemic.

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Section: Interaction Network Reveals the Imbalance Of Biological Procsupporting

confidence: 88%

Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples

Leng

Cao²,

et al. 2020

Sig Transduct Target Ther

167

131

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“…Given both the scarcity of human clinical specimens (e.g. lung IPF biopsies) and the discordance in the expression of lung cathepsins and their endogenous inhibitors between murine bleomycin-induced fibrosis and human pulmonary fibrosis 40 , human CCD-19Lu fibroblasts appeared to be a pertinent model to decipher molecular mechanisms and signaling pathways associated with human pulmonary myofibrogenesis 29 . A hallmark in the development of fibrosis is the TGF-β1-dependent activation, proliferation and differentiation of fibroblasts to α-SMA-expressing myofibroblasts that secrete excessive amounts of collagen.…”

Section: Resultsmentioning

confidence: 99%

Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L

Saidi

Kasabova

Vanderlynden

et al. 2019

Sci Rep

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Pulmonary fibrosis is a progressive disease characterized by a widespread accumulation of myofibroblasts and extracellular matrix components. Growing evidences support that cysteine cathepsins, embracing cathepsin B (CatB) that affects TGF-β1-driven Smad pathway, along with their extracellular inhibitor cystatin C, participate in myofibrogenesis. Here we established that curcumin, a potent antifibrotic drug used in traditional Asian medicine, impaired the expression of both α-smooth muscle actin and mature TGF-β1 and inhibited the differentiation of human lung fibroblasts (CCD-19Lu cells). Curcumin induced a compelling upregulation of CatB and CatL. Conversely cystatin C was downregulated, which allowed the recovery of the peptidase activity of secreted cathepsins and the restoration of the proteolytic balance. Consistently, the amount of both insoluble and soluble type I collagen decreased, reaching levels similar to those observed for undifferentiated fibroblasts. The signaling pathways activated by curcumin were further examined. Curcumin triggered the expression of nuclear peroxisome proliferator-activated receptor γ (PPARγ). Contrariwise PPARγ inhibition, either by an antagonist (2-chloro-5-nitro-N-4-pyridinyl-benzamide) or by RNA silencing, restored TGF-β1-driven differentiation of curcumin-treated CCD-19Lu cells. PPARγ response element (PPRE)-like sequences were identified in the promoter regions of both CatB and CatL. Finally, we established that the transcriptional induction of CatB and CatL depends on the binding of PPARγ to PPRE sequences as a PPARγ/Retinoid X Receptor-α heterodimer.

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“…Additionally, cathepsin K knock-out mice deposited more extracellular matrix and had decreased collagenolytic activity, which points to an important role of cathepsin K in lung collagenolytic activity [168,169]. The same model also provided evidence for cathepsin B overexpression and presence in BALF [170]. Furthermore, cathepsin S was shown to cleave decorin and produce a fragment, which can be robustly detected in the serum of fibrosis and cancer patients [94].…”

Section: Ecm Proteolysis and The Cathepsinsmentioning

confidence: 99%

Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment

Vidak

Javoršek

Vizovišek

et al. 2019

Cells

307

228

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: For a long time, cysteine cathepsins were considered primarily as proteases crucial for nonspecific bulk proteolysis in the endolysosomal system. However, this view has dramatically changed, and cathepsins are now considered key players in many important physiological processes, including in diseases like cancer, rheumatoid arthritis, and various inflammatory diseases. Cathepsins are emerging as important players in the extracellular space, and the paradigm is shifting from the degrading enzymes to the enzymes that can also specifically modify extracellular proteins. In pathological conditions, the activity of cathepsins is often dysregulated, resulting in their overexpression and secretion into the extracellular space. This is typically observed in cancer and inflammation, and cathepsins are therefore considered valuable diagnostic and therapeutic targets. In particular, the investigation of limited proteolysis by cathepsins in the extracellular space is opening numerous possibilities for future break-through discoveries. In this review, we highlight the most important findings that establish cysteine cathepsins as important players in the extracellular space and discuss their roles that reach beyond processing and degradation of extracellular matrix (ECM) components. In addition, we discuss the recent developments in cathepsin research and the new possibilities that are opening in translational medicine.

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Discordance in cathepsin B and cystatin C expressions in bronchoalveolar fluids between murine bleomycin-induced fibrosis and human idiopathic fibrosis

Cited by 12 publications

References 19 publications

Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples

Pathological features of COVID-19-associated lung injury: a preliminary proteomics report based on clinical samples

Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L

Cysteine Cathepsins and Their Extracellular Roles: Shaping the Microenvironment

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