Reduced expression of collagen VI alpha 3 (COL6A3) confers resistance to inflammation‐induced MCP1 expression in adipocytes

Abstract

Objective: Collagen VI alpha 3 (COL6A3) is associated with insulin resistance and adipose tissue inflammation. In this study, the role of COL6A3 in human adipocyte function was characterized. Methods: Immortalized human preadipocyte cell lines stably expressing control or COL6A3 shRNA were used to study adipocyte function and inflammation. Results: COL6A3 knockdown increased triglyceride content, lipolysis, insulin-induced Akt phosphorylation, and mRNA expression of key adipogenic genes (peroxisome proliferator-activated receptor-c, glucose transporter, adiponectin, and fatty acid binding protein), indicating increased adipocyte function and insulin sensitivity. However, COL6A3 knockdown decreased basal adipocyte chemokine (C-C motif) ligand 2 [CCL2, monocyte chemoattractant protein (MCP1)] mRNA expression, reduced secreted protein levels, and abrogated tumor necrosis factor-a-and lipopolysaccharide-induced MCP1 mRNA expression. In addition, while control adipocytes co-cultured with THP1 macrophages showed a threefold increase in adipocyte MCP1 mRNA expression, in COL6A3 knockdown adipocytes MCP1 mRNA expression was unaltered by co-culturing. Lastly, in normal differentiated adipocytes, matrix metalloproteinase-11 treatment reduced expression of COL6A3 protein, MCP1 mRNA, MCP1 secretion, and abrogated tumor necrosis factor-a-and lipopolysaccharide-induced MCP1 mRNA expression and protein secretion. Conclusions: COL6A3 knockdown in adipocytes leads to the development of a unique state of inflammatory resistance via suppression of MCP1 induction.

Retracted: Silencing of COL1A2, COL6A3, and THBS2 inhibits gastric cancer cell proliferation, migration, and invasion while promoting apoptosis through the PI3k‐Akt signaling pathway

“…As TGF‐b helps activate the PI3K signaling pathway, we believe that COL1A2 silencing may down‐regulate TGF‐b in cancer cells and inhibit the activation of PI3K signaling pathway. A decreased expression of COL6A3 (Collagen IV) was involved in the inflammation‐resistance process and helped to increase the content of triglyceride while promoting lipolysis and the phosphorylation of Akt . By inhibiting MCP1 expression, the PI3K/Akt signaling pathway was downregulated, thus leading to the promotion of the tumor cell apoptosis process .…”

“…A decreased expression of COL6A3 (Collagen IV) was involved in the inflammation-resistance process and helped to increase the content of triglyceride while promoting lipolysis and the phosphorylation of Akt. 17 By inhibiting MCP1 expression, the PI3K/Akt signaling pathway was downregulated, thus leading to the promotion of the tumor cell apoptosis process. 30 Additionally, Kim et al 31 observed that THBS2 influences the proteolysis of tumor cytoplasm, thus contributing to the activation and expression of certain proteins in the PI3K/Akt signaling pathway.…”

Plasma PTX3, MCP1 and Ang2 are early biomarkers to evaluate the severity of sepsis and septic shock

“…Several studies have reported that MCP1 also had the ability to regulate inflammatory progression and the production of pro-inflammatory cytokines in adipocytes, ankylosing spondylitis and cancer. [30][31][32] Our results showed a positive correlation between plasma MCP1 and cytokines (TNF-α, IL-6, IL-8 and IL-10) in sepsis. Moreover, Zhu T et al found that plasma MCP1 maybe a useful biomarker in predicting the prognosis of sepsis.…”

“…This study demonstrated that plasma MCP1 levels presented significant and valuable AUCs for discriminating septic shock from healthy and post‐surgery controls. Several studies have reported that MCP1 also had the ability to regulate inflammatory progression and the production of pro‐inflammatory cytokines in adipocytes, ankylosing spondylitis and cancer . Our results showed a positive correlation between plasma MCP1 and cytokines (TNF‐α, IL‐6, IL‐8 and IL‐10) in sepsis.…”

Local effects of adipose tissue in psoriasis and psoriatic arthritis

“…Very recently, it was demonstrated that COL6a3 knockdown in adipocytes leads to inflammatory resistance by the suppression of monocyte chemoattractant protein 1, which points to an interconnection between COL6 and inflammation. 91 While systemic modification of COL6 content was shown to be generally connected with MetS, 92 local modification of the adipose tissue ECM can be assumed to be significant in some skin pathologies. It was also shown that cathelicidin regulates myeloid cell accumulation in WAT and can thus promote insulin resistance.…”