Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice

Sun, Wenchang; Yan, Shushan; Yang, Chunjuan; Yang, Jinghan; Wang, Hui; Li, Chaoran; Zhang, Lili; Zhao, Lu; Zhang, Jiaojiao; Cheng, Min; Li, Xiangling; Xu, Dongmei

doi:10.1080/08820139.2022.2055478

Cited by 25 publications

(20 citation statements)

References 54 publications

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“…These results are consistent with this study. 14 The PPI network was composed of 36 nodes and 50 edges, utilizing the CytoHubba plug-in to screen for potential hub genes, successfully yielding the following three key genes: BMPR2, SMAD5, and ATF2.…”

Section: Discussionmentioning

confidence: 99%

Identify the influences of systemic lupus erythematosus on acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura using comprehensive bioinformatics analysis

Zhang

2023

Lupus

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Background The association between acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura (aTTP) and systemic lupus erythematosus (SLE) has been studied; however, the underlying molecular causes remain poorly understood. This research aimed to employ bioinformatics approaches to elucidate potential molecular mechanisms contributing to the pathogenesis of SLE and aTTP. Material and methods The Gene Expression Omnibus (GEO) database yielded GSE121239 and GSE36418 to get mutual different expression genes (DEGs). Subsequently, DEGs were subjected to process Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, the DEGs were used for protein–protein interaction (PPI) analysis and screened for hub genes and drugs by the DGIDB drug database. Results A total of 87 DEGs between the SLE and TTP datasets were identified. In the GO and KEGG analyses, DEGs were mainly enriched in the “regulation of transcription by RNA polymerase II” and “signaling pathways regulating pluripotency of stem cells.” After a PPI analysis, three hub genes (BMPR2, SMAD5, and ATF2) were identified. Finally, two drugs targeted to ATF2 were predicted by the DGIDB drug database. Conclusions Three core genes were linked to the molecular pathogenesis of SLE and aTTP, and two drugs may be viable treatments for both diseases.

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Section: Discussionmentioning

confidence: 99%

Identify the influences of systemic lupus erythematosus on acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura using comprehensive bioinformatics analysis

Zhang

2023

Lupus

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“…39 The imbalance of M1/ M2 macrophages and cytokines is collectively involved in the progression of LN. [40][41][42] Some researchers have shown that M1 macrophages mainly played a role in promoting inflammation and fibrosis, while the M2 macrophages were capable of an anti-inflammatory effect and promoted the repair and reconstruction process of damaged tissues. 43 Kidney damage in LN was related to the infiltration of M1 macrophages by secreting IFN-γ, which could act as an inflammatory factor to up-regulate the inflammatory immune response.…”

Section: Discussionmentioning

confidence: 99%

FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway

Zuo,

Pan,

Wang

et al. 2023

Lupus

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Background Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE), and its pathogenesis is not fully understood. Previously, we showed that fractalkine (FKN) expression was positively correlated with the severity of LN. Here, we aimed to study the role of the Hippo signaling pathway (HSP) and its interaction with FKN in LN in an attempt to provide novel strategies for LN treatment. Methods In this study, lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-stimulated THP-1 cells were co-cultured with FKN up-regulated or down-regulated kidney epithelial cells Hkb20. FKN-knockout (KO-FKN) mice were used to construct LN model. Flow cytometric analysis, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), pathological staining, Western blot, and immunofluorescence (IF) staining were employed to investigate the role of FKN and its interaction with the Hippo signaling pathway (HSP) in LN. Results Up-regulation of FKN in kidney epithelial cells was associated with increased macrophage activation. FKN overexpression in kidney epithelial cells suppressed apoptosis, inflammation levels, and M1 polarization of THP-1 cells and inhibited the HSP. Oppositely, FKN knockdown in kidney epithelial cells increased apoptosis, inflammation, and M1 polarization and activated the HSP. HSP inhibitor reversed the effect of FKN knockdown on THP-1 cells. In LN mice, FKN knockout and YAP inhibitor decreased the levels of renal function markers, alleviated kidney injury induced by LN, and inhibited macrophage activation in LN mice. Conclusions FKN down-regulation reduced the activation of macrophages in renal tissue and alleviated kidney damage by activating HSP. The regulatory effect of FKN on HSP should be confirmed in patients with LN, and the mechanism of FKN in LN should be further explored.

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“…However, the gene expression profiles of affected skin, lung, esophagus and peripheral blood in patients with SSc showed that the expression of M2-related genes was significantly up-regulated in macrophages with pronounced fibrogenic effect ( 162 ). Infiltrated macrophages in skin lesions from SSc and local scleroderma were found to highly express CD163 ( 163 – 165 ), indicating that M2 macrophage may also involve in skin fibrosis. Besides, studies have found that some biological agents can inhibit the process of SSc by reversing the polarization of M2 macrophages.…”

Section: Macrophages In Sscmentioning

confidence: 99%

Macrophage: Key player in the pathogenesis of autoimmune diseases

2023

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The macrophage is an essential part of the innate immune system and also serves as the bridge between innate immunity and adaptive immune response. As the initiator and executor of the adaptive immune response, macrophage plays an important role in various physiological processes such as immune tolerance, fibrosis, inflammatory response, angiogenesis and phagocytosis of apoptotic cells. Consequently, macrophage dysfunction is a vital cause of the occurrence and development of autoimmune diseases. In this review, we mainly discuss the functions of macrophages in autoimmune diseases, especially in systemic lupus erythematosus (SLE), rheumatic arthritis (RA), systemic sclerosis (SSc) and type 1 diabetes (T1D), providing references for the treatment and prevention of autoimmune diseases.

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Mesenchymal Stem Cells-derived Exosomes Ameliorate Lupus by Inducing M2 Macrophage Polarization and Regulatory T Cell Expansion in MRL/lpr Mice

Cited by 25 publications

References 54 publications

Identify the influences of systemic lupus erythematosus on acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura using comprehensive bioinformatics analysis

Identify the influences of systemic lupus erythematosus on acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura using comprehensive bioinformatics analysis

FKN secreted by kidney epithelial cells regulates macrophage activation in lupus nephritis via the Hippo signaling pathway

Macrophage: Key player in the pathogenesis of autoimmune diseases

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