Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type

Ding, Liqing; Li, Xiaojing; Zhu, Honglin; Luo, Hui

doi:10.14336/ad.2022.0323

Cited by 4 publications

(4 citation statements)

References 113 publications

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“…CTHRC1 protein levels were also significantly greater in the serum of RA patients than in that of healthy individuals [72]. Similar to what was found in mice, CTHRC1 expression was elevated in two subpopulations of synoviocytes isolated from the pannus of RA patients, one of which was strongly linked to disease pathology [74]. Therefore, CTHRC1 may contribute to cartilage degradation in individuals with RA by modulating the migration and invasion of a pathological synoviocyte subpopulation.…”

Section: Cthrc1-structural Characteristics Expression and Disease Rel...supporting

confidence: 73%

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

Mukhatayev,

Adilbayeva,

Kunz

2024

Cells

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Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.

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Section: Cthrc1-structural Characteristics Expression and Disease Rel...supporting

confidence: 73%

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

Mukhatayev,

Adilbayeva,

Kunz

2024

Cells

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“…One subtype was characterized by the CD34+ CDH11+ THY1/CD90-phenotype and was proposed to recruit monocytes via IL-6, CXCL12, and CCL2. Another phenotype included the expression of CD34− CDH11+ THY1/CD90+, and this subtype was strongly linked with RA pathology [53]. In addition, both subsets also expressed several other genes related to migration and invasion, including TWIST1, POSTN, LOXL2, PDGFRB, and MMP14 [54,55], and these activities were confirmed in vitro.…”

Section: Cthrc1 As a Biomarker For Ramentioning

confidence: 81%

CTHRC1: An Emerging Biomarker in Lung Fibrosis

Mukhatayev,

Adilbayeva,

Kunz

2023

Preprint

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Pulmonary fibrosis is a chronic, progressive, and irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (EM) due to a persistently activated wound-repair response. The aberrant activation of myofibroblasts in the alveolar environment by Transforming Growth Factor beta (TGF-β) and other signaling molecules is considered a key event in the development and progression of fibrosis. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in extracellular matrix deposition. CTHRC1 is transcriptionally regulated by TGF-β and inhibits both TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 is vital in regulating tissue remodeling during wound repair. In this review, we will highlight recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, rheumatoid arthritis-interstitial lung disease, systemic sclerosis, and post-COVID lung fibrosis. Notably, the expression of CTHRC1 is responsive to antifibrotic drugs such as pirfenidone indicating its potential as a therapeutic target. Collectively, these findings suggest that CTHRC1 may present new opportunities for the diagnosis, stratification, and treatment of patients with lung fibrosis.

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“…The single cell sequencing could be used for the functional analysis of candidate genes in human diseases at a single cell level [ 18 – 20 ]. The correlation heatmap between MTF1 expression and functional status were obtained from CancerSEA [ 21 ] ( http://biocc.hrbmu.edu.cn/CancerSEA/ ).…”

Section: Methodsmentioning

confidence: 99%

The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma

et al. 2023

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Metal regulatory transcription factor 1 (MTF1) has been reported to be correlated with several human diseases, especially like cancers. Exploring the underlying mechanisms and biological functions of MTF1 could provide novel strategies for clinical diagnosis and therapy of cancers. In this study, we conducted the comprehensive analysis to evaluate the profiles of MTF1 in pan-cancer. For example, TIMER2.0, TNMplot and GEPIA2.0 were employed to analyze the expression values of MTF1 in pan-cancer. The methylation levels of MTF1 were evaluated via UALCAN and DiseaseMeth version 2.0 databases. The mutation profiles of MTF1 in pan-cancers were analyzed using cBioPortal. GEPIA2.0, Kaplan–Meier plotter and cBioPortal were also used to explore the roles of MTF1 in cancer prognosis. We found that high MTF1 expression was related to poor prognosis of liver hepatocellular carcinoma (LIHC) and brain lower grade glioma (LGG). Also, high expression level of MTF1 was associated with good prognosis of kidney renal clear cell carcinoma (KIRC), lung cancer, ovarian cancer and breast cancer. We investigated the genetic alteration and methylation levels of MTF1 between the primary tumor and normal tissues. The relationship between MTF1 expression and several immune cells was analyzed, including T cell CD8 + and dendritic cells (DC). Mechanically, MTF1-interacted molecules might participate in the regulation of metabolism-related pathways, such as peptidyl-serine phosphorylation, negative regulation of cellular amide metabolic process and peptidyl-threonine phosphorylation. Single cell sequencing indicated that MTF1 was associated with angiogenesis, DNA repair and cell invasion. In addition, in vitro experiment indicated knockdown of MTF1 resulted in the suppressed cell proliferation, increased reactive oxygen species (ROS) and promoted cell death in LIHC cells HepG2 and Huh7. Taken together, this pan-cancer analysis of MTF1 has implicated that MTF1 could play an essential role in the progression of various human cancers.

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Single-Cell Sequencing in Rheumatic Diseases: New Insights from the Perspective of the Cell Type

Cited by 4 publications

References 113 publications

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

CTHRC1: An Emerging Biomarker in Lung Fibrosis

The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma

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