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Cadmium-mediated miR-30a-GRP78 leads to JNK-dependent autophagy in chicken kidney

Qunxiang Shi1, Xi Jin1, Ruifeng Fan1

  • 1College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.

Chemosphere
|October 24, 2018
PubMed

Insights

Cadmium exposure in chickens disrupts kidney function by affecting microRNA-30a and GRP78, leading to endoplasmic reticulum stress and autophagy. Selenium supplementation mitigates these cadmium-induced negative effects.

Area of Science:

  • Environmental Toxicology
  • Molecular Biology
  • Animal Science

Background:

  • Cadmium (Cd) is a toxic heavy metal that accumulates in organs like the kidney.
  • MicroRNAs (miRNAs) play roles in cellular processes, including autophagy and endoplasmic reticulum (ER) stress.
  • The specific mechanisms of Cd-induced kidney damage via miRNAs, particularly in poultry, require further investigation.

Purpose of the Study:

  • To elucidate the relationship between miR-30a, GRP78, ER stress, and autophagy in chicken kidneys under Cd exposure.
  • To investigate the role of the IRE-1-JNK pathway in Cd-induced kidney damage.
  • To evaluate the protective effects of selenium (Se) against Cd toxicity in chicken kidneys.

Main Methods:

  • 128 Hy-Line Brown laying chickens were divided into four groups: control, Se, Se + Cd, and Cd.
  • Dietary treatments involved different levels of sodium selenite (Na2SeO3) and cadmium chloride (CdCl2).
  • Gene and miRNA expression (miR-30a, GRP78, ER stress markers, IRE-1-JNK, autophagy markers) were analyzed on day 90.

Main Results:

  • Cd exposure significantly increased IRE-1-JNK, ER stress, and autophagy-related gene expression while decreasing miR-30a expression in chicken kidneys.
  • Cd exposure led to a significant increase in GRP78 expression.
  • Selenium supplementation alleviated the Cd-induced changes, indicating a protective effect.

Conclusions:

  • Cadmium exposure triggers an miR-30a-GRP78 signaling axis disorder, exacerbating ER stress and activating the IRE-1-JNK pathway, which promotes autophagy in chicken kidneys.
  • Selenium antagonizes the adverse effects of cadmium on kidney function.
  • This study highlights the intricate molecular mechanisms of Cd toxicity and the potential of Se as a counteracting agent in poultry.
Keywords:
AutophagyCadmiumER stressJNKmiR-30a-GRP78

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