Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

Wang, Jing; Zhang, Xinxin; Min, Long; Yuan, Mengqin; Yin, Juan; Luo, Wei; Wang, Sha; Cai, Yu; Jiang, Wei; Chao, Jie

doi:10.1038/s42003-022-04333-5

Cited by 12 publications

(9 citation statements)

References 42 publications

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“…CD44 participates in a wide variety of cellular functions, including lymphocyte activation, recirculation, and homing [32][33][34], alongside CD31 being an alternative pathway for leukocyte extravasation to the lung compartment [26]. CD44 pathway may be important in the development of fibrosis [35]. Culty et al had shown that CD44 expression is greater in the area of granuloma formation and fibrosis [36].…”

Section: Discussionmentioning

confidence: 99%

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

Danila¹,

Aleksonienė²,

Besusparis³

et al. 2023

Preprint

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The search for biological markers, which allow a relatively accurate assessment of the individual course of pulmonary sarcoidosis at the time of diagnosis remains one of the research priorities in this field of pulmonary medicine. The aim of our study was to investigate possible prognostic factors for pulmonary sarcoidosis with a special focus on cellular immune inflammation markers. 2 years follow-up of the study population after initial prospective and simultaneous analysis of lymphocyte activation markers expression in the blood, as well as bronchoalveolar lavage fluid (BALF), and lung biopsy tissue of patients with newly diagnosed pulmonary sarcoidosis, was done. We found that some blood and BAL fluid immunological markers and lung computed tomography (CT) patterns have been associated with a different course of sarcoidosis. We revealed five markers that had a significant negative association with the course of sarcoidosis (worsening pulmonary function tests and/or the chest CT changes) – blood CD4+CD31+ and CD4+CD44+ T lymphocytes, BALF CD8+CD31+ and CD8+CD103+ T lymphocytes and a number of lung nodules on chest CT at the time of the diagnosis. Cut-off values, sensitivity, specificity, and odds ratio for predictors of sarcoidosis progression were calculated. These markers may be reasonable predictors of sarcoidosis progression.

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Section: Discussionmentioning

confidence: 99%

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

Danila¹,

Aleksonienė²,

Besusparis³

et al. 2023

Preprint

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“…The fibrotic matrix traps GPNMB and encourages fibroblast movement and PF via the CD44/Serpinb2 pathway. 123 8.1. Limitations, Key Findings, and Future Insights.…”

Section: Decellularized Tissue Matrixes/acellular Ex Vivo Lung Slicesmentioning

confidence: 99%

“…The potential causes of alterations were determined by RNA sequencing and transcriptomic analysis that revealed worsening ECM directly impairs fibroblast activity (Figure b). The fibrotic matrix traps GPNMB and encourages fibroblast movement and PF via the CD44/Serpinb2 pathway …”

Section: Decellularized Tissue Matrixes/acellular Ex Vivo Lung Slicesmentioning

confidence: 99%

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

Jain,

Shashi Bhushan,

Natarajan

et al. 2024

ACS Biomater. Sci. Eng.

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Fibrosis has been characterized as a global health problem and ranks as one of the primary causes of organ dysfunction. Currently, there is no cure for pulmonary fibrosis, and limited therapeutic options are available due to an inadequate understanding of the disease pathogenesis. The absence of advanced in vitro models replicating dynamic temporal changes observed in the tissue with the progression of the disease is a significant impediment in the development of novel antifibrotic treatments, which has motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends in preparing advanced lung models to recapitulate biochemical and biomechanical processes associated with lung fibrogenesis. We begin by describing the importance of in vivo studies and highlighting the often poor correlation between preclinical research and clinical outcomes and the limitations of conventional cell culture in accurately simulating the 3D tissue microenvironment. Rapid advancement in biomaterials, biofabrication, biomicrofluidics, and related bioengineering techniques are enabling the preparation of in vitro models to reproduce the epithelium structure and operate as reliable drug screening strategies for precise prediction. Improving and understanding these model systems is necessary to find the cross-talks between growing cells and the stage at which myofibroblasts differentiate. These advanced models allow us to utilize the knowledge and identify, characterize, and hand pick medicines beneficial to the human community. The challenges of the current approaches, along with the opportunities for further research with potential for translation in this field, are presented toward developing novel treatments for pulmonary fibrosis.

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“…However, a dysregulated response can result in persistent in ammation and maladaptive regeneration, ultimately leading to tissue-destructive brosis. Previous studies have indicated that, in a chronic in ammatory environment, the GPNMB secreted by macrophages can stimulate excessive deposition of ECM, ultimately leading to pulmonary brosis 35 . After skeletal muscle injury, macrophages play a key role in clearing apoptotic cells and aiding tissue regeneration, a process that involves the conversion of in ltrating monocytes to macrophages with in ammatory and regenerative phenotypes.…”

Section: Identi Cation Of Ve Distinct Macrophage Subsets During Skele...mentioning

confidence: 99%

Temporal Single-Cell Sequencing Analysis Reveals That GPNMB-Expressing Macrophages Potentiate Muscle Regeneration

Chen

2024

Preprint

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Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. To address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Gpnmb and that coexpressed critical factors involved in macrophage-mediated muscle regeneration, including Igf1, Mertk, and Nr1h3. Gpnmb gene knockout inhibited macrophage-mediated efferocytosis and impaired skeletal muscle regeneration. Functional studies demonstrated that GPNMB acts directly on muscle cells in vitro and improves muscle regeneration in vivo. These findings provide a comprehensive transcriptomic atlas of macrophages during muscle injury, highlighting the key role of the GPNMB macrophage subset in regenerative processes. Targeting GPNMB signaling in macrophages could have therapeutic potential for restoring skeletal muscle integrity and homeostasis.

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Macrophage-derived GPNMB trapped by fibrotic extracellular matrix promotes pulmonary fibrosis

Cited by 12 publications

References 42 publications

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

CD4+CD31+ and CD4+CD44+ Lymphocytes in Peripheral Blood, CD8+CD31+ and CD8+CD103+ Lymphocytes in Bronchoalveolar Lavage Fluid, and Pulmonary Nodules in Predicting the Course of Pulmonary Sarcoidosis

Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

Temporal Single-Cell Sequencing Analysis Reveals That GPNMB-Expressing Macrophages Potentiate Muscle Regeneration

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