Trichostatin A Alleviates Renal Interstitial Fibrosis Through Modulation of the M2 Macrophage Subpopulation

Autor: Nien Jung Chen, Der Cherng Tarng, Wei Cheng Tseng, Ming Tsun Tsai
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
030232 urology & nephrology
Hydroxamic Acids
trichostatin A
Article
Catalysis
Cell Line
Proinflammatory cytokine
Inorganic Chemistry
lcsh:Chemistry
Mice
03 medical and health sciences
0302 clinical medicine
Fibrosis
medicine
Renal fibrosis
Animals
Renal Insufficiency
Chronic
Physical and Theoretical Chemistry
Myofibroblasts
Molecular Biology
lcsh:QH301-705.5
Cells
Cultured
Spectroscopy
Kidney
Chemistry
Macrophages
Organic Chemistry
General Medicine
macrophage subpopulation
medicine.disease
M2 Macrophage
renal fibrosis
Rats
Computer Science Applications
Histone Deacetylase Inhibitors
Mice
Inbred C57BL
030104 developmental biology
Trichostatin A
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
Histone deacetylase
Myofibroblast
medicine.drug
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 5966, p 5966 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 17
ISSN: 1661-6596
1422-0067
Popis: Mounting evidence indicates that an increase in histone deacetylation contributes to renal fibrosis. Although inhibition of histone deacetylase (HDAC) can reduce the extent of fibrosis, whether HDAC inhibitors exert the antifibrotic effect through modulating the phenotypes of macrophages, the key regulator of renal fibrosis, remains unknown. Moreover, the functional roles of the M2 macrophage subpopulation in fibrotic kidney diseases remain incompletely understood. Herein, we investigated the role of HDAC inhibitors on renal fibrogenesis and macrophage plasticity. We found that HDAC inhibition by trichostatin A (TSA) reduced the accumulation of interstitial macrophages, suppressed the activation of myofibroblasts and attenuated the extent of fibrosis in obstructive nephropathy. Moreover, TSA inhibited M1 macrophages and augmented M2 macrophage infiltration in fibrotic kidney tissue. Interestingly, TSA preferentially upregulated M2c macrophages and suppressed M2a macrophages in the obstructed kidneys, which was correlated with a reduction of interstitial fibrosis. TSA also repressed the expression of proinflammatory and profibrotic molecules in cultured M2a macrophages and inhibited the activation of renal myofibroblasts. In conclusion, our study was the first to show that HDAC inhibition by TSA alleviates renal fibrosis in obstructed kidneys through facilitating an M1 to M2c macrophage transition.
Databáze: OpenAIRE
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