Autoimmune Disorders in Galectin-3 Deficient Mice

Author(s):  
Vladislav Volarevic ◽  
Miodrag L. Lukic
2019 ◽  
Vol 116 (3) ◽  
pp. 721-735 ◽  
Author(s):  
Francisco J Rios ◽  
Zhi-Guo Zou ◽  
Adam P Harvey ◽  
Katie Y Harvey ◽  
Ryszard Nosalski ◽  
...  

Abstract Aims Transient Receptor Potential Melastatin 7 (TRPM7) cation channel is a chanzyme (channel + kinase) that influences cellular Mg2+ homeostasis and vascular signalling. However, the pathophysiological significance of TRPM7 in the cardiovascular system is unclear. The aim of this study was to investigate the role of this chanzyme in the cardiovascular system focusing on inflammation and fibrosis. Methods and results TRPM7-deficient mice with deletion of the kinase domain (TRPM7+/Δkinase) were studied and molecular mechanisms investigated in TRPM7+/Δkinase bone marrow-derived macrophages (BMDM) and co-culture systems with cardiac fibroblasts. TRPM7-deficient mice had significant cardiac hypertrophy, fibrosis, and inflammation. Cardiac collagen and fibronectin content, expression of pro-inflammatory mediators (SMAD3, TGFβ) and cytokines [interleukin (IL)-6, IL-10, IL-12, tumour necrosis factor-α] and phosphorylation of the pro-inflammatory signalling molecule Stat1, were increased in TRPM7+/Δkinase mice. These processes were associated with infiltration of inflammatory cells (F4/80+CD206+ cardiac macrophages) and increased galectin-3 expression. Cardiac [Mg2+]i, but not [Ca2+]i, was reduced in TRPM7+/Δkinase mice. Calpain, a downstream TRPM7 target, was upregulated (increased expression and activation) in TRPM7+/Δkinase hearts. Vascular functional and inflammatory responses, assessed in vivo by intra-vital microscopy, demonstrated impaired neutrophil rolling, increased neutrophil: endothelial attachment and transmigration of leucocytes in TRPM7+/Δkinase mice. TRPM7+/Δkinase BMDMs had increased levels of galectin-3, IL-10, and IL-6. In co-culture systems, TRPM7+/Δkinase macrophages increased expression of fibronectin, proliferating cell nuclear antigen, and TGFβ in cardiac fibroblasts from wild-type mice, effects ameliorated by MgCl2 treatment. Conclusions We identify a novel anti-inflammatory and anti-fibrotic role for TRPM7 and suggest that its protective effects are mediated, in part, through Mg2+-sensitive processes.


2010 ◽  
Vol 185 (2) ◽  
pp. 1205-1214 ◽  
Author(s):  
Xiao Na Ge ◽  
Nooshin S. Bahaie ◽  
Bit Na Kang ◽  
M. Reza Hosseinkhani ◽  
Sung Gil Ha ◽  
...  

2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Camila Brand ◽  
Thayse Pinheiro da Costa ◽  
Emerson Soares Bernardes ◽  
Camila Maria Longo Machado ◽  
Leonardo Rodrigues Andrade ◽  
...  

2009 ◽  
Vol 50 (12) ◽  
pp. 5690 ◽  
Author(s):  
Chandrassegar Saravanan ◽  
Zhiyi Cao ◽  
Steven R. Head ◽  
Noorjahan Panjwani

Glycobiology ◽  
2013 ◽  
Vol 23 (6) ◽  
pp. 654-663 ◽  
Author(s):  
A. C. MacKinnon ◽  
X. Liu ◽  
P. W. Hadoke ◽  
M. R. Miller ◽  
D. E. Newby ◽  
...  

2016 ◽  
Vol 84 (4) ◽  
pp. 1184-1193 ◽  
Author(s):  
Ah-Mee Park ◽  
Satoru Hagiwara ◽  
Daniel K. Hsu ◽  
Fu-Tong Liu ◽  
Osamu Yoshie

We studied the role of galectin-3 (Gal3) in gastric infection byHelicobacter pylori. We first demonstrated that Gal3 was selectively expressed by gastric surface epithelial cells and abundantly secreted into the surface mucus layer. We next inoculatedH. pyloriSydney strain 1 into wild-type (WT) and Gal3-deficient mice using a stomach tube. At 2 weeks postinoculation, the bacterial cells were mostly trapped within the surface mucus layer in WT mice. In sharp contrast, they infiltrated deep into the gastric glands in Gal3-deficient mice. Bacterial loads in the gastric tissues were also much higher in Gal3-deficient mice than in WT mice. At 6 months postinoculation,H. pylorihad successfully colonized within the gastric glands of both WT and Gal3-deficient mice, although the bacterial loads were still higher in the latter. Furthermore, large lymphoid clusters mostly consisting of B cells were frequently observed in the gastric submucosa of Gal3-deficient mice.In vitro, peritoneal macrophages from Gal3-deficient mice were inefficient in killing engulfedH. pylori. Furthermore, recombinant Gal3 not only induced rapid aggregation ofH. pyloribut also exerted a potent bactericidal effect onH. pylorias revealed by propidium iodide uptake and a morphological shift from spiral to coccoid form. However, a minor fraction of bacterial cells, probably transient phase variants of Gal3-binding sugar moieties, escaped killing by Gal3. Collectively, our data demonstrate that Gal3 plays an important role in innate immunity to infection and colonization ofH. pylori.


2009 ◽  
Vol 29 (6) ◽  
pp. 831-836 ◽  
Author(s):  
Carla Iacobini ◽  
Stefano Menini ◽  
Carlo Ricci ◽  
Angela Scipioni ◽  
Viola Sansoni ◽  
...  
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