Cathepsin G increases MMP expression in normal human fibroblasts through fibronectin fragmentation, and induces the conversion of proMMP-1 to active MMP-1

Son, Eui Dong; Kim, Hyaekyoung; Choi, Hyunjung; Lee, So Hee; Lee, Jin Young; Kim, Su-Jung; Closs, B.; Lee, Sera; Chung, Jin Ho; Hwang, Jae Sung

doi:10.1016/j.jdermsci.2008.08.006

Cited by 35 publications

(43 citation statements)

References 7 publications

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“…KPA (fig. 1a), a non-peptide type inhibitor of cathepsin G [20], reduces both the fragmentation of Fn and the conversion of proMMP-1 to active MMP-1 in cathepsin G-treated NHFs [19], which is in line with our findings. The IC 50 of KPA for cathepsin G was 38 n M , while that for elastase was over 20 µ M (the maximal KPA concentration tested) (fig.…”

Section: Resultssupporting

confidence: 91%

“…Previously, we reported that cathepsin G increased MMP-1 expression through Fn fragmentation [19]. Cathepsin G also induced the conversion of proMMP-1 to active MMP-1 in NHFs, resulting in the acceleration of ECM degradation [19].…”

Section: Discussionmentioning

confidence: 99%

“…Cathepsin G also induced the conversion of proMMP-1 to active MMP-1 in NHFs, resulting in the acceleration of ECM degradation [19]. Importantly, KPA ameliorated cathepsin G-mediated MMP activation and the downregulation of collagen mRNA expression in an in vitro 3D DE model as well as in an in vivo photoaging model.…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated that the expression of cathepsin G is higher in aged human skin compared with young skin, and its activity increases in UVA (5 J/cm 2 )-irradiated NHFs compared with non-irradiated NHFs [19]. The mechanism of action of cathepsin G encompasses the degradation of Fn into four or five Fn-frs.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism of action of cathepsin G encompasses the degradation of Fn into four or five Fn-frs. Among these, a 45-kDa collagen-binding Fn-fr (Fn-f45) and a 70-kDa N-terminal heparin/gelatin-binding Fn-fr (Fn-f70) have been shown to increase matrix metalloproteinase-1 (MMP-1) expression and the actions of proMMP-2 and active MMP-2 [19]. Furthermore, cathepsin G induced the conversion of proMMP-1 to active MMP-1 in NHFs [19], again suggesting a critical role of cathepsin G in photoaging.…”

Section: Introductionmentioning

confidence: 99%

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Cathepsin G Inhibitor Prevents Ultraviolet B- Induced Photoaging in Hairless Mice via Inhibition of Fibronectin Fragmentation

et al. 2012

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Background: Cathepsin G, a serine protease that is activated by ultraviolet (UV) radiation, increases matrix metalloproteinase-1 (MMP-1) expression in fibroblasts through fibronectin (Fn) fragmentation and promotes the conversion of proMMP-1 to active MMP-1. Objectives: This study investigated whether [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA), a cathepsin G inhibitor, plays any role in extracellular matrix (ECM) damage in an in vitro 3D dermal equivalent (DE) and an in vivo ultraviolet B (UVB)-irradiated hairless mice. Methods: We examined the potential ECM-protective effects of a cathepsin G inhibitor in an in vitro 3D DE model and an in vivo UVB-irradiated hairless mouse skin model. Results: Among five known serine protease inhibitors, KPA showed the strongest potency and selectivity against cathepsin G. KPA inhibited the cathepsin G-mediated MMP-1 increase and alleviated the downregulation of mRNAs encoding collagen and tissue inhibitor of matrix metalloproteinase-1 in an in vitro 3D DE model. Most importantly, topical application of KPA (0.025%) to the dorsal skin of hairless mice enhanced collagen expression and attenuated UVB-induced Fn fragmentation and upregulation of MMP-2 and MMP-9 activities. Conclusions: Cathepsin G inhibitors may be useful for the prevention of UVB-induced photoaging through amelioration of ECM damage and MMP upregulation.

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Section: Resultssupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cathepsin G Inhibitor Prevents Ultraviolet B- Induced Photoaging in Hairless Mice via Inhibition of Fibronectin Fragmentation

et al. 2012

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A Tandem‐Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy

Cheng

Zhang

et al. 2023

Angewandte Chemie

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NETosis, the peculiar type of neutrophil death, plays important roles in pro‐tumorigenic functions and inhibits cancer immunotherapy. Non‐invasive real‐time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem‐locked NETosis Reporter 1 (TNR1) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker‐specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem‐locked design allows TNR1 to differentiate NETosis from neutrophil activation, while single‐locked reporters fail to do so. The near‐infrared signals from activated TNR1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near‐infrared signals from activated TNR1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor‐bearing living mice, but also proposes a generic approach for tandem‐locked probe design.

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A Tandem‐Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy

Cheng

Zhang

et al. 2023

Angew Chem Int Ed

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NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1 (TNR 1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarkerspecific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem-locked design allows TNR 1 to differentiate NETosis from neutrophil activation, while single-locked reporters fail to do so. The near-infrared signals from activated TNR 1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near-infrared signals from activated TNR 1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor-bearing living mice, but also proposes a generic approach for tandem-locked probe design.

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Cathepsin G increases MMP expression in normal human fibroblasts through fibronectin fragmentation, and induces the conversion of proMMP-1 to active MMP-1

Cited by 35 publications

References 7 publications

Cathepsin G Inhibitor Prevents Ultraviolet B- Induced Photoaging in Hairless Mice via Inhibition of Fibronectin Fragmentation

Cathepsin G Inhibitor Prevents Ultraviolet B- Induced Photoaging in Hairless Mice via Inhibition of Fibronectin Fragmentation

A Tandem‐Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy

A Tandem‐Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy

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