Effects of high glucose on proliferation and function of circulating fibrocytes: Involvement of CXCR4/SDF‑1 axis

Abstract

The present study aimed to further investigate the effects of high glucose on the function of circulating fibrocytes and its underlying mechanisms. The total peripheral blood mononuclear cells were obtained from normal glucose tolerance patients and type 2 diabetic mellitus patients. Circulating fibrocytes were stimulated with different glucose concentrations for different time periods (24, 48 and 72 h). Cell proliferation was determined by Cell Counting Kit-8 assay. The expression of connective tissue growth factor (CTGF) was detected by western blotting. The expression of COL-I was detected by flow cytometry. The apoptotic bodies of cells were detected by fluorescence microscopy after Hoechst33258 staining. The invasive and migration abilities of fibrocytes were detected by Transwell chamber assay. Secretion of stromal cell-derived factor 1 (SDF-1) was measured by ELISA. The circulating fibrocytes showed a typical spindle-shape and were double-positive for cluster of differentiation 45 (green) and COL-I (red). Compared with the 5.5 mmol/l glucose group, a high glucose concentration significantly promoted the proliferation of circulating fibrocytes and showed the most significant effects at 30 mmol/l after treatment for 48 h. AMD3100 showed no effects on the proliferation of circulating fibrocytes. Flow cytometry revealed that 30 mmol/l glucose significantly promoted the expression of COL-I vs. 5.5 mmol/l glucose group (P<0.01), while AMD3100 reversed this (P<0.05). Hoechst33258 staining showed no differences in the apoptotic bodies between experimental groups (P>0.05). Western blotting revealed that the expression of CTGF was decreased significantly by AMD3100 pretreatment (P<0.01). Transwell chamber assay showed that 30 mmol/l glucose significantly promoted the invasive and transfer abilities (P<0.01) of fibrocytes when compared with the 5.5 mmol/l glucose group. While AMD3100 reversed the cell migratory effects induced by high glucose (P<0.01). In addition, the secretion of SDF-1 stimulated by 30 mmol/l glucose DMEM showed no differences compared with 5.5 mmol/l glucose DMEM (P>0.05). High glucose stimulated the expressions of CTGF and COL-I, and promoted migration of circulating fibrocytes via the CXC chemokine receptor 4/SDF-1 axis.

Hypoxia-induced miR-210 modulates the inflammatory response and fibrosis upon acute ischemia

“…Fibrocytes appear to differentiate from peripheral blood monocytes 47 , bear characteristics of both fibroblasts and monocytes and are able to differentiate in myofibroblast-like cells increasing their expression of TGFβ and endothelin 25 . Interestingly, fibrocytes might play a crucial role in organ fibrosis through the CXC chemokine receptor 4 (CXCR4)/stromal‑derived factor‑1 (SDF‑1 α/CXCL12) axis 48 and we previously demonstrated that miR-210 over-expression enhance circulating pro-angiogenic cell migration toward SDF-1 α/CXCL12 49 .…”

Ibudilast, a Phosphodiesterase-4 Inhibitor, Ameliorates Acute Respiratory Distress Syndrome in Neonatal Mice by Alleviating Inflammation and Apoptosis

“…The chemokine receptor4 (CXCR4)/stromal-derived factor-1 (SDF-1) chemokine axis plays key roles in inflammation of injured tissues. Activation of the CXCR4/SDF-1 axis can lead to interstitial lung fibrosis or other lung disease [26]. CXCR5, expressed by vascular endothelium, is reported to regulate inflammation by affecting leucocyte migration [27].…”

Dysregulated Dermal Mesenchymal Stem Cell Proliferation and Differentiation Interfered by Glucose Metabolism in Psoriasis

“…The Virgintino et al ( 32 ) supported that in human brain, CXCL12/CXCR7 system appears to be directly involved in microvessel growth, its members being differentially expressed in angiogenically activated microvessels and vascular sprouts. Weng et al ( 33 ) showed that CXCR4/SDF 1 axis was involvement the effects of high glucose on proliferation and function of circulating fibrocytes. RGS5 (regulator of G protein signalling 5) is correlated with vascular abnormalities ( 34 ).…”