Macrophage phenotype and its relationship with renal function in human diabetic nephropathy

PLoS One. 2019 Sep 11;14(9):e0221991. doi: 10.1371/journal.pone.0221991. eCollection 2019.

Abstract

This study aimed to examine the macrophage phenotype and its relationship to renal function and histological changes in human DN and the effect of TREM-1 on high-glucose-induced macrophage activation. We observed that in renal tissue biopsies, the expression of CD68 and M1 was apparent in the glomeruli and interstitium, while accumulation of M2 and TREM-1 was primarily observed in the interstitium. The numbers of CD68, M1, and M2 macrophages infiltrating in the DN group were increased in a process-dependent manner compared with the control group, and the intensities of the infiltrates were proportional to the rate of subsequent decline in renal function. M1 macrophages were recruited into the kidney at an early stage (I+IIa) of DN. The M1-to-M2 macrophage ratio peaked at this time, whereas M2 macrophages predominated at later time points (III) when the percentage of M1/M2 macrophages was at its lowest level. In an in vitro study, we showed that under high glucose conditions, macrophages began to up-regulate their expression of TREM-1, M1, and marker iNOS and decreased the M2 marker MR. However, the above effects of high-glucose were abolished when TREM-1 expression was inhibited by TREM-1 siRNA. In conclusion, our study demonstrated that there was a positive correlation between the M1/M2 activation state and the progress of DN, and TREM-1 played an important role in high-glucose-induced macrophage phenotype transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology*
  • Gene Expression Regulation / drug effects
  • Glucose / pharmacology*
  • Humans
  • Kidney Function Tests
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide Synthase Type II
  • Phenotype
  • RAW 264.7 Cells
  • Triggering Receptor Expressed on Myeloid Cells-1 / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • TREM1 protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Glucose

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81570612 and No. 81870497), Clinical Medical Science Technology Special Project of Jiangsu Province (No. BL2014080). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.