Regulator of Cell Cycle Protein (RGCC/RGC-32) Protects against Pulmonary Fibrosis

Luzina, Irina G.; Rus, Violeta; Lockatell, Virginia; Courneya, Jean-Paul; Hampton, Brian; Fishelevich, Rita; Misharin, Alexander V.; Todd, Nevins W.; Badea, Tudor C.; Rus, Horea; Atamas, Sergei P.

doi:10.1165/rcmb.2021-0022oc

Cited by 8 publications

(5 citation statements)

References 49 publications

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“… 42 , 43 Intriguingly, it has been proposed from a recent study that RGCC exerts a protective function in pulmonary fibrosis, with its downregulation leading to collagen accumulation. 44 RGCC overexpression delayed early TGF-β-induced Smad2/3 phosphorylation, increased the expression of total and phosphorylated antifibrotic mediator STAT1, and reduced the expression of the profibrotic mediator STAT3. 44 RGCC ’s roles extend beyond endothelial cells and encompass immune cells as well.…”

Section: Discussionmentioning

confidence: 90%

“… 44 RGCC overexpression delayed early TGF-β-induced Smad2/3 phosphorylation, increased the expression of total and phosphorylated antifibrotic mediator STAT1, and reduced the expression of the profibrotic mediator STAT3. 44 RGCC ’s roles extend beyond endothelial cells and encompass immune cells as well. In T-lymphocytes, RGCC serves as a negative cell cycle regulator.…”

Section: Discussionmentioning

confidence: 90%

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Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Zhu,

Deng

2024

CCID

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Background Systemic sclerosis represents a persistent autoimmune disorder marked with fibrosis affecting both skin and other organs, which leads to a diminished quality of life and increased mortality. The affected skin provides a valuable opportunity to explore the pathogenesis of systemic sclerosis. Nevertheless, the roles of various cell populations within scleroderma remain intricate. Methods We conducted a comprehensive reanalysis of recently published single-cell RNA-sequencing data from skin tissue cells in scleroderma. Through the utilization of Seurat, irGSEA, AUCell packages, and WGCNA analysis, we aimed to unveil crucial genes associated with the disease’s etiological factors. Our investigation involved the characterization of heterogeneous pathway activities in both healthy and SSc-affected skin. Furthermore, we employed immunofluorescence techniques to validate the expression patterns of hub genes and differentially expressed genes. Results The Endothelial-to-Mesenchymal Transition (EndMT) pathway was upregulated in SSc skin. Notably, the M4 module within Endothelial cell subpopulation 1 exhibited a strong association with EndMT. Furthermore, we identified three overexpressed genes ( APLNR , I NS-IGF2, RGCC ) that demonstrated a significant correlation with EndMT. Importantly, their expression levels were markedly higher in skin of individuals with SSc when compared to healthy controls. Conclusion APLNR, INS-IGF2 and RGCC serve as potential key players in the pathogenesis of SSc skin through EndMT-dependent mechanisms.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Zhu,

Deng

2024

CCID

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“…Of note, these top-downregulated genes in COVID-19 fibroblasts are mainly members of the SFTP family, which have been proved to be markers of alveolar structure and lung epithelial cells [ 13 ]. Meanwhile, RGCC (Regulator of Cell Cycle), SPRY2 (Sprouty RTK Signaling Antagonist 2), and FTH1 (Ferritin Heavy Chain 1) were also significantly downregulated, and they have been verified to negatively regulate fibroblast growth factor or proliferation [ 25 – 27 ]. These results further revealed that fibrosis of COVID-19 patients can be induced by EMT accompanied by a significantly increased EMT score (Fig.…”

Section: Resultsmentioning

confidence: 99%

Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients

Qin

Yao

et al. 2023

Cell Death Dis

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How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell’s activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

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“…One gene that has emerged as a critical player in various disease processes is the response gene to complement (RGC)-32. It has been implicated in tumorigenesis, astrocytosis, extracellular matrix deposition, pulmonary fibrosis, T lymphocyte cell cycle regulation, and Th17 cell differentiation in experimental autoimmune encephalomyelitis (7)(8)(9). For example, Cui et al demonstrated that RGC-32 deficiency can suppress hepatic steatosis by reducing lipogenesis (10).…”

Section: Introductionmentioning

confidence: 99%

RGC-32 facilitates pancreatic cancer via activating Wnt/β-catenin signaling

Jinli He,

Guihong Yang,

Ronglai Cao

et al. 2023

Cell Mol Biol (Noisy-le-grand)

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Regulator of Cell Cycle Protein (RGCC/RGC-32) Protects against Pulmonary Fibrosis

Cited by 8 publications

References 49 publications

Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Single-Cell RNA-Sequencing Analyses Identify APLNR, INS-IGF2, RGCC Genes May Be Involved in the Pathogenesis of Systemic Sclerosis Skin

Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients

RGC-32 facilitates pancreatic cancer via activating Wnt/β-catenin signaling

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