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


Autoři: Xiaoliang Zhang aff001;  Ying Yang aff001;  Yu Zhao aff001
Působiště autorů: Institute of Nephrology, Zhong Da Hospital, Southeast University, School of Medicine, Nanjing, Jiangsu, China aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0221991

Souhrn

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.

Klíčová slova:

Biology and life sciences – Cell biology – Cellular types – Animal cells – Blood cells – White blood cells – Macrophages – Immune cells – Genetics – Gene expression – Gene regulation – Small interfering RNAs – Phenotypes – Biochemistry – Nucleic acids – RNA – Non-coding RNA – Anatomy – Renal system – Kidneys – Physiology – Developmental biology – Molecular development – Medicine and health sciences – Immunology – Immune system – Innate immune system – Cytokines – Endocrinology – Endocrine disorders – Metabolic disorders – Immune physiology – Physical sciences – Chemistry – Chemical compounds – Organic compounds – Carbohydrates – Monosaccharides – Glucose – Organic chemistry


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