MiR-214-3p exacerbates kidney damages and inflammation induced by hyperlipidemic pancreatitis complicated with acute renal injury

Life Sci. 2020 Jan 15:241:117118. doi: 10.1016/j.lfs.2019.117118. Epub 2019 Nov 29.

Abstract

Aims: Acute pancreatitis (AP) is usually complicated with multiple organ insufficiency, including renal injury. Hyperlipidemia is regarded as a risk factor to induce AP. High-fat diet-induced hyperlipidemic pancreatitis (HP) increased nowadays and showed more severe symptoms and complications than other AP. However, detailed mechanisms or mediators involved in HP complicated with acute renal injury were less studied. Here, we aimed to study how miR-214 expresses in the HP and whether miR-214 has functions to regulate pathological kidney damages induced by HP.

Main methods: Sprague-Dawley rats were adopted to establish HP model complicated with acute renal injury through long-term high-fat diet and sodium taurocholic injection. Models were injected with LV-rno-miR-214-3p or LV-anti-rno-miR-214-3p to exogenously regulate miR-214-3p to study its impacts on HP via a series of molecular and histological experiments.

Key findings: MiR-214-3p was found to be up-regulated in the kidney, pancreas and serum of HP rats and also could intensify the pathological alterations, kidney and pancreas damages and fibrosis induced by HP. Inflammatory response in HP was enhanced when miR-214-3p was overexpressed. Besides, miR-214-3p up-regulation was showed to inhibit PTEN expression but increased P-Akt levels in the HP kidney, which might be a possible mechanism to induce severe symptoms of pancreatitis. Knockdown of miR-214-3p showed opposite effects.

Significance: MiR-214-3p is indicated to exacerbate the tissue damages and inflammatory response caused by HP complicated with acute renal injury, which may provide a novel therapeutic perspective targeting miR-214-3p to treat HP with acute renal injury.

Keywords: Acute renal injury; Hyperlipidemic pancreatitis; Inflammation; MiR-214; PTEN.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Amylases / blood
  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hyperlipidemias / complications*
  • Hyperlipidemias / genetics
  • Kidney / pathology
  • Lipids / blood
  • Lipids / genetics
  • Male
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Pancreatitis / complications*
  • Pancreatitis / genetics
  • Pancreatitis / pathology
  • Rats, Sprague-Dawley

Substances

  • Lipids
  • MicroRNAs
  • Mirn214 microRNA, rat
  • PTEN Phosphohydrolase
  • Pten protein, rat
  • Amylases