In our study, we found that purified HBV significantly increased HMC proliferation, and also increased expression levels of type IV collagen and FN. The major mechanism of increased HMC proliferation and extracellular matrix expression in HBV-GN is suggested to be due to HBV immune complex deposition [6, 9]. However, many studies have detected HBV DNA, as both free and integrated forms, in mesangial cells. He et al. have reported that the expression of HBV DNA in the nucleus and cytoplasm of HMCs in HBV-GN patients verified the presence of HBV DNA in HMC . Wang et al. showed that HBV DNA as the integrated form was detected in 82% (41/50) of cases in HMCs by in situ hybridization . These observations suggest that HBV DNA can infect HMCs, and that it can directly induce pathological alterations in HMCs that might be involved in HBV-GN . However, these studies were all conducted in renal tissues, and the effects of HBV on HMCs were suggested to be a result of immune complex formation in situ[7, 11]. Because of confounding factors involving immune complexes that are circulating, it was difficult to show whether HBV can directly affect HMCs in these studies. In our study, we purified HBV from the sera of HBV-infected patients. The HMCs were co-cultured with purified HBV in vitro, thereby overcoming the confounding factors related to the immune complex, and we showed that purified HBV directly affected HMCs.
There were some limitations to our study. We did not explore the mechanisms through which HBV increased HMC proliferation and expression of extracellular matrix proteins. HBV X Protein (HBx) acts an indirect transcriptional transactivitor to regulate cell proliferation, transdifferentiation and apoptosis . Some studies have shown that HBx can induce mesangial cell proliferation through the upregulation of interleukin-1β and interleukin-6 . However, in these previous studies, HBx was transfected into mesangial cells artificially; therefore, it remains unknown whether HBV can induce HMC proliferation through a natural infection. Further studies will be required to clarify this.
In conclusion, our findings support the hypothesis that HBV exerts direct effects on HMCs, and will hopefully enrich our understanding of the pathogenesis of HBV-GN.