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Abstract: SA-PO1103

A Vicious Cycle of Steroid Therapy, Hyperlipidemia, and Macrophage Activation in the Progression of Chronic Renal Lesions

Session Information

Category: Pathology and Lab Medicine

  • 1502 Pathology and Lab Medicine: Clinical

Authors

  • Ikezumi, Yohei, Fujita Health University School of Medicine, Toyoake, Japan
  • Matsumoto, Yuji, Fujita Health University School of Medicine, Toyoake, Japan
  • Kondo, Tomomi, Fujita Health University School of Medicine, Toyoake, Japan
  • Hasegawa, Hiroya, Niigata University Medical and Dental Hospital, Niigata-City, Niigata, Japan
  • Yamada, Takeshi, Niigata University Medical and Dental Hospital, Niigata-City, Niigata, Japan
  • Nikolic-Paterson, David J., Monash Medical Centre, Clayton, Victoria, Australia
Background

We have previously reported that increasing numbers of LDL-scavenger receptor (SR)+ macrophages (MQ) is a feature of refractory nephrotic syndrome (RNS) in hyperlipidemic patients treated with high-dose glucocorticoids. To investigate potential pathogenic mechanisms, we examined how glucocorticoids and hyperlipidemia alter the function of human MQ.

Methods

Normal human monocyte-derived MQ (huMQ) were incubated with dexamethasone (Dex), or oxidized LDL (oxLDL) or both, for 48 hours and then analysed by DNA microarray.

Results

Dex and/or ox-LDL stimulation induced up-regulation of scavenger receptors characteristic of M2-type MQ (CD163, CD204 and CD36). Dex and/or ox-LDL also induced up-regulation of cytokines and growth factors associated with inflammation and fibrosis (CCL2, CXCL13, NOS2, TGF-β1, FGF-1, FGF-2 and VEGF-D). In addition, a change in MQ metabolism is suggested altered expression of glucokinase regulator, aldose reductase and acetyl-CoA carboxylase. Immunohistochemistry revealed significant expression of FGF1 in biopsies from RNS patients with RNS which co-localized with CD204+ MQ in areas of fibrosis.

Conclusion

Our data suggest that a vicious cycle of steroid therapy, hyperlipidemia, and M2-type MQ activation promote the progression of renal chronic lesions and treatment resistance.

Funding

  • Government Support - Non-U.S.