Mechanism of miR-365 in regulating BDNF-TrkB signal axis of HFD/STZ induced diabetic nephropathy fibrosis and renal function.

Abstract

PURPOSE:

Diabetic nephropathy (DN) is one of the most serious complications of diabetes that leads to decline of renal function. Although numerous studies have revealed that microRNAs (miRNAs) play essential roles in the progression of DN, whether miR-365 is involved remains elusive.

METHODS:

The successful construction of DN model was confirmed by ELSIA, hematoxylin-eosin (HE) and Masson staining assay. The expression of miR-365 was detected through RT-qPCR. The levels of BDNF, p-TrkB, α-smooth muscle actin (SMA), collagen IV (Col.IV), transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were evaluated by western blot, IF or ELISA assays. Luciferase reporter assay was used to detect the interaction between miR-365 and BDNF.

RESULTS:

The DN mice model was induced by streptozotocin (STZ). Then miR-365 expression was found to upregulate in tissues of DN rat. Furthermore, elevated expression of miR-365 was found in high glucose (HG)-treated HK-2 cells. Silencing of miR-365 suppressed the accumulation of ECM components and secretion of inflammatory cytokines in HK-2 cells. In addition, it was demonstrated that miR-365 could target BDNF. The protein levels of BDNF and p-TrkB were negatively regulated by miR-365 in HK-2 cells. Moreover, inhibition of miR-365 suppressed the levels of SMA, Col.IV, TGF-β1, TNF-α, and IL-6, indicating the renal fibrosis was inhibited by miR-365 knockdown.

CONCLUSION:

MiR-365 could regulate BDNF-TrkB signal axis in STZ induced DN fibrosis and renal function. The results of the current study might provide a promising biomarker for the treatment of DN in the future.

• Authors: Peng Zhao, Xiaqiu Li, Yang Li, Jiaying Zhu, Yu Sun, Jianli Hong
• Journal: International urology and nephrology (Int Urol Nephrol) Vol. 53 Issue 10 Pg. 2177-2187 (Oct 2021) ISSN: 1573-2584 [Electronic] Netherlands
• PMID: 33881703 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• Brain-Derived Neurotrophic Factor
• MIRN365 microRNA, mouse
• Membrane Glycoproteins
• MicroRNAs
• Ntrk2 protein, mouse
• Protein-Tyrosine Kinases

Topics

• Animals
• Brain-Derived Neurotrophic Factor (physiology)
• Cells, Cultured
• Diabetes Mellitus, Experimental (complications, physiopathology)
• Diabetic Nephropathies (complications, physiopathology)
• Fibrosis (etiology)
• Humans
• Kidney (pathology, physiopathology)
• Male
• Membrane Glycoproteins (physiology)
• Mice
• MicroRNAs (physiology)
• Protein-Tyrosine Kinases (physiology)
• Rats
• Rats, Sprague-Dawley