Circulating miR-103a-3p contributes to angiotensin II-induced renal inflammation and fibrosis via a SNRK/NF-κB/p65 regulatory axis

• Published in: Nature communications 2019-05, Vol.10 (1), p.2145-2145, Article 2145
• Main Authors: Lu, Qiulun, Ma, Zejun, Ding, Ye, Bedarida, Tatiana, Chen, Liming, Xie, Zhonglin, Song, Ping, Zou, Ming-Hui
• Format: Article
• Language: English
• Subjects: 45; 45/88; 631/337/384/331; 692/4022/1585/3182; Adult; Angiotensin; Angiotensin II; Angiotensin II - administration & dosage; Angiotensin II - metabolism; Animals; Case-Control Studies; Cells, Cultured; Disease Models, Animal; Endothelial cells; Female; Fibrosis; Glomerulonephritis - blood; Glomerulonephritis - genetics; Glomerulonephritis - pathology; Glomerulonephritis - urine; Healthy Volunteers; Humanities and Social Sciences; Humans; Hypertension, Renal - blood; Hypertension, Renal - genetics; Hypertension, Renal - pathology; Hypertension, Renal - urine; Inflammation; Kidney Glomerulus - cytology; Kidney Glomerulus - pathology; Kinases; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs - blood; MicroRNAs - metabolism; MicroRNAs - urine; Middle Aged; multidisciplinary; Nephritis - blood; Nephritis - genetics; Nephritis - pathology; Nephritis - urine; Nephropathy; NF-κB protein; Primary Cell Culture; Protein kinase; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Renal function; Science; Science (multidisciplinary); Sucrose; Sugar; Threonine; Transcription Factor RelA - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-10116-0

Although angiotensin II (AngII) is known to cause renal injury and fibrosis, the underlying mechanisms remain poorly characterized. Here we show that hypertensive nephropathy (HN) patients and AngII-infused mice exhibit elevated levels of circulating miR103a-3p. We observe a positive correlation between miR-103a-3p levels and AngII-induced renal dysfunction. miR-103a-3p suppresses expression of the sucrose non-fermentable-related serine/threonine-protein kinase SNRK in glomerular endothelial cells, and glomeruli of HN patients and AngII-infused mice show reduced endothelial expression of SNRK. We find that SNRK exerts anti-inflammatory effects by interacting with activated nuclear factor-κB (NF-κB)/p65. Overall, we demonstrate that AngII increases circulating miR-103a-3p levels, which reduces SNRK levels in glomerular endothelial cells, resulting in the over-activation of NF-κB/p65 and, consequently, renal inflammation and fibrosis. Together, our work identifies miR-103a-3p/SNRK/NF-κB/p65 as a regulatory axis of AngII-induced renal inflammation and fibrosis. Angiotensin II is known to cause renal inflammation and fibrosis. Here Lu et al. show that levels of circulating miR-103a-3p are elevated in hypertensive nephropathy patients and in an animal model of angiotensin II-induced renal dysfunction, and that miR-103a-3p suppresses SNRK expression leading to the activation of the pro-inflammatory NF-κB pathway in glomerular endothelial cells.