CXCL10 expression induced by Mxi1 inactivation induces mesangial cell apoptosis in mouse Habu nephritis

Wu, Lingling; Chen, Xiaoniao; Mei, Yan; Hong, Quan; Feng, Zhe; Lv, Yang; Wen, Jun; Liu, Xiaoluan; Cai, Guangyan

doi:10.1016/j.cellsig.2015.01.019

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…In contrast with above findings, our colleagues Wu et al [27] proposed that CXCL10 expression induced by Mxi1 inactivation leads to mesangial cell apoptosis in murine Habu nephritis. They used Mxi1-deficient mice to generate a Habu nephritis model and found a high CXCL10 expression in the mesangial dissolution period, which promoted apoptosis by activating caspase 3.…”

Section: Mesangial Proliferative Glomerulonephritis (Mespgn)contrasting

confidence: 60%

“…The antifibrotic effects of CXCL10 in myocardial infarction are independent of CXCR3 and may be mediated through proteoglycan signaling [25]. In addition, CXCL10 induces β cell apoptosis by binding to TLR4 in pancreatic β cells [26], and the TLR4-IRF3 pathway is involved in regulating CXCL10 expression in the Habu nephritis model [27]. Interestingly, there is evidence for CXCL10 signaling independent of binding to CXCR3 or GAGs that might be related to epithelial and endothelial cell function, but the exact mechanism has not yet been described [5,28].…”

Section: Chemokine Cxcl10 and Its Receptor Cxcr3mentioning

confidence: 99%

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Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Gao

Wang

et al. 2020

Mediators of Inflammation

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Chemokine C–X–C ligand 10 (CXCL10), also known as interferon-γ-inducible protein 10 (IP-10), exerts biological function mainly through binding to its specific receptor, CXCR3. Studies have shown that renal resident mesangial cells, renal tubular epithelial cells, podocytes, endothelial cells, and infiltrating inflammatory cells express CXCL10 and CXCR3 under inflammatory conditions. In the last few years, strong experimental and clinical evidence has indicated that CXCL10 is involved in the development of renal diseases through the chemoattraction of inflammatory cells and facilitation of cell growth and angiostatic effects. In addition, CXCL10 has been shown to be a significant biomarker of disease severity, and it can be used as a prognostic indicator for a variety of renal diseases, such as renal allograft dysfunction and lupus nephritis. In this review, we summarize the structures and biological functions of CXCL10 and CXCR3, focusing on the important role of CXCL10 in the pathogenesis of kidney disease, and provide a theoretical basis for CXCL10 as a potential biomarker and therapeutic target in human kidney disease.

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Section: Mesangial Proliferative Glomerulonephritis (Mespgn)contrasting

confidence: 60%

Section: Chemokine Cxcl10 and Its Receptor Cxcr3mentioning

confidence: 99%

Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Gao

Wang

et al. 2020

Mediators of Inflammation

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“…In previous study, Wu L et al [39] used Mxi1-deficient mice, which were on FVB/N background, to generate Habu nephritis model and found that Mxi1 inactivation induced the expression of CXCL10 and aggravated the mesangial cell apoptosis. Habu nephritis mouse model is characterized by mesangiolysis and mesangial proliferation.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Gao¹,

Wang

et al. 2017

Cell Physiol Biochem

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Background/Aims: IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in chemotaxis, cell growth regulation and angiogenesis inhibition. It has been reported that CXCL10 expression is significantly increased in patients with MesPGN (Mesangial proliferative glomerulonephritis). However, the underlying mechanism of CXCL10 in MesPGN reminds unclear. Methods: Wildtype (Cxcl10^+/+) mice and Cxcl10-deficient (Cxcl10^-/-) mice were used to generate a murine model of MesPGN. The histological changes in glomeruli were examined by PAS staining (Periodic Acid-Schiff staining), and cell proliferation was detected by PCNA immunohistochemistry staining. The expression of cell cycle regulatory proteins was analyzed by Western blotting and the effects of CXCL10 on primary mouse renal mesangial cells (MRMC) proliferation were detected using the EDU assay. Furthermore, the specific mechanisms by which CXCL10 affected mesangial cells were investigated in vitro using a specific inhibitor. Results: Typical pathological phenotypes were observed in both mouse types, while the Cxcl10^-/- mice had lighter accumulation of extracellular matrix, less cell proliferation and diminished up-regulation of cell cycle regulatory proteins compared to Cxcl10^+/+ mice at day 7. Furthermore, we observed that CXCL10 inhibition resulted in less activation of ERK phosphorylation, and ERK pathway inhibition by a specific inhibitor, U0126, prevented CXCL10 induced MRMC proliferation and the activation of phosphorylated ERK. Conclusions: CXCL10 may aggravate mesangial proliferation in MesPGN by activating the ERK signaling pathway. These results provide a novel insight into the mechanism and potential therapy target of MesPGN.

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“… 30 , 31 Habu snake venom (HSV) was used to induce the mouse model of MesPGN. 32 , 33 To improve the success rate of modeling, HSV was injected twice through the caudal vein. Normal rats were injected with normal saline.…”

Section: Methodsmentioning

confidence: 99%

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis

Zhou

Zhang³

et al. 2022

IJN

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Purpose Mesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity. Hence, specific co-delivery of “anti-inflammatory/anti-fibrosis” drugs to the glomerular mesangial cell (MC) region is expected to produce better therapeutic effects. Methods A novel kidney-targeted nanocarrier drug delivery system targeting MCs was constructed using passive targeting resulting from the difference in pore size between the glomerular endothelial layer and the basement membrane, and active targeting based on the specific binding of antibodies and antigens. Specifically, a liposome-nanoparticle hybrid (PLGA-LNHy) was formed by coating the surface of PLGA nanoparticles (NPs) with a phospholipid bilayer, and then PLGA-LNHy was co-modified with PEG and α8 integrin antibodies to obtain PLGA immunoliposomes (PLGA-ILs). Results The results showed that the obtained NPs had a core-shell structure, uniform and suitable particle size (119.1 ± 2.31 nm), low cytotoxicity, and good mesangial cell-entry ability, which can successfully accumulate in the glomerular MC region. Both dexamethasone (DXMS) and captopril (CAP) were loaded onto PLGA-ILs with a drug loading of 10.22 ± 1.00% for DXMS and 6.37 ± 0.25% for CAP (DXMS/CAP@PLGA-ILs). In vivo pharmacodynamics showed that DXMS/CAP@PLGA-ILs can effectively improve the pathological changes in the mesangial area and positive expression of proliferating cell nuclear antigen (PCNA) in glomeruli as well as reduce the expression of inflammatory factors, fibrotic factors and reactive oxygen species (ROS). Thus, renal inflammation and fibrosis were relieved. Conclusion We have provided a strategy to increase nanoparticle accumulation in MCs with the potential to implement regulatory effects of anti-inflammatory and anti-fibrosis in glomerulonephritis (GN).

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CXCL10 expression induced by Mxi1 inactivation induces mesangial cell apoptosis in mouse Habu nephritis

Cited by 6 publications

References 35 publications

Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Role of Chemokine (C–X–C Motif) Ligand 10 (CXCL10) in Renal Diseases

Knockdown of Cxcl10 Inhibits Mesangial Cell Proliferation in Murine Habu Nephritis Via ERK Signaling

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis

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