Effects Of HMGB1 On Proliferation, Collagen Types â…  And â…¢ Mrna Expression In Cardiac Fibroblasts

High-mobility group box 1 (HMGB1) protein is one of the recently defined damage-associated molecular pattern molecules, ubiquitously present in all vertebrate nucleiit, conbstablizes nucleosomes and enables bending of DNA, which facilitates gene transcription. Strikingly, once released , it plays roles in many situations, especially in inflammatory response and cytokine elaboration, serving as a late mediator of systemic inflammation. Recently, it has been reported that the HMGB1 level from the serum in patients with myocardial infarction was significantly increased and HMGB1 is well associated with the cardiac remodeling after myocardial infarction. The cardiac remodeling, in response to pathological changes such as myocardial infarction, refers to myocardial hypertrophy, proliferation of interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix. The interstitial fibroblasts and concomitant increased biosynthesis of extracellular matrix is associated with not only decreased quality of life but also an increased incidence of heart failure and stroke and should be paid more attention to. Objective:Objective to investigate the effects of HMGB1 on the proliferation and synthesis of collagen in cultured rat cardiac fibroblasts and evaluate its potential role in the process of cardiac remodeling after myocardial infarction.Methods:1 . Cardiac fibroblasts were isolated from neonatal Sprague-Dawley rat ,cultured and divided into 4 groups. They were treated in vitro with 0(control group), 0.01, 0.1 and 1mg/L HMGB1 respectively. After 6, 12, 18, 24 and 48 hours of treatment of HMGB1, the proliferation of CFs from four groups was determined by MTT assay, PCNA protein expression was assessed by Western blot, and Real-time quantitative RT-PCR was done to assess the mRNA expression of collagen I and III.Results:1..In contrast to the control group, the proliferation level and PCNA protein expression in HMGB1 treated groups were significantly up-regulated after 48hrs of treatment(p<0.05); 2.We observed an HMGB1 concentration-dependent increase of proliferation and PCNA protein levels(p<0.05). The highest level of proliferation and PCNA protein expression is in 0.1mg/L group althouth only HMGB1 at a concentration of 1mg/L showed weaker effect; 3.The mRNA expression of collagen I and III was up-regulated in HMGB1 treated groups after 48hrs(p<0.05); 4. The HMGB1-induced increase of collagen I and III mRNA expression was also concentration-dependent with the same weaker effect in 1mg/L group. And the expression of collagen I and III was highest in 0.1mg/L group. No significant statistical difference was observed in HMGB1 treatment. Conclusion:The present data suggests that HMGB1 can increase the proliferation , PCNA protein expression, and collagen I and III mRNA expression of neonatal Sprague-Dawley rat cardiac fibroblasts in a concentration-dependent manner to some extent and HMGB1 may play an important role in cardiac remodeling after myocardial infarction. However, if HMGB1 works the same way in vivo needs further investigation.