<p>Polyacrylic acid (PAA) is a widely used organic polymer synthesized from acrylic acid monomers. Its viscosity and water absorbency can be modified through cross-linking, making it suitable for various applications, including shampoos, food products, and pharmaceuticals. However, several reports have suggested that PAA has high potential for pulmonary injury, especially if exposed during product manufacturing processes. To elucidate which specific physicochemical properties of PAA lead to pulmonary disease development, we intratracheally instilled PAA with different physicochemical properties in rats. We compared the lung responses of standard PAA containing carboxyl groups (COOH) and specially manufactured COOH-removed PAA. Male F344 rats were intratracheally instilled with COOH-removed PAA at two doses (0.2&#xa0;mg, 1.0&#xa0;mg/rat), standard PAA with COOH at one dose (1.0&#xa0;mg/rat), or distilled water (control group). Inflammatory and fibrotic responses in the lungs were examined at 3&#xa0;days, 1&#xa0;week, 1&#xa0;month, 3&#xa0;months, and 6&#xa0;months post-exposure. PAA with COOH group exhibited persistent pulmonary inflammation and fibrosis, whereas the COOH-removed PAA showed no detectable signs of either condition. Comprehensive analyses of lung tissue mRNA revealed significantly increased Spp1 expression in the PAA with COOH group compared with the COOH-removed PAA group. Comprehensive analyses of microRNAs in bronchoalveolar lavage fluid extracellular vesicles revealed decreased expression of miR-23a-3p and miR-24-3p, which are associated with pulmonary fibrosis. Analysis of human datasets provided additional support for our animal findings. Our results indicate that the COOH in PAA is involved in lung inflammation and fibrosis through specific changes in gene expression.</p>

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Pulmonary responses to polyacrylic acid with and without carboxyl groups following intratracheal instillation in rats

  • Toshiki Morimoto,
  • Hiroto Izumi,
  • Chinatsu Nishida,
  • Taisuke Tomonaga,
  • Yuiko Nakamura,
  • Yasuyuki Higashi,
  • Ke-Yong Wang,
  • Takuma Kojima,
  • Kazuo Sakurai,
  • Akihiro Moriyama,
  • Jun-ichi Takeshita,
  • Hidenori Higashi,
  • Masahiro Tahara,
  • Kei Yamasaki,
  • Kazuhiro Yatera,
  • Yasuo Morimoto

摘要

Polyacrylic acid (PAA) is a widely used organic polymer synthesized from acrylic acid monomers. Its viscosity and water absorbency can be modified through cross-linking, making it suitable for various applications, including shampoos, food products, and pharmaceuticals. However, several reports have suggested that PAA has high potential for pulmonary injury, especially if exposed during product manufacturing processes. To elucidate which specific physicochemical properties of PAA lead to pulmonary disease development, we intratracheally instilled PAA with different physicochemical properties in rats. We compared the lung responses of standard PAA containing carboxyl groups (COOH) and specially manufactured COOH-removed PAA. Male F344 rats were intratracheally instilled with COOH-removed PAA at two doses (0.2 mg, 1.0 mg/rat), standard PAA with COOH at one dose (1.0 mg/rat), or distilled water (control group). Inflammatory and fibrotic responses in the lungs were examined at 3 days, 1 week, 1 month, 3 months, and 6 months post-exposure. PAA with COOH group exhibited persistent pulmonary inflammation and fibrosis, whereas the COOH-removed PAA showed no detectable signs of either condition. Comprehensive analyses of lung tissue mRNA revealed significantly increased Spp1 expression in the PAA with COOH group compared with the COOH-removed PAA group. Comprehensive analyses of microRNAs in bronchoalveolar lavage fluid extracellular vesicles revealed decreased expression of miR-23a-3p and miR-24-3p, which are associated with pulmonary fibrosis. Analysis of human datasets provided additional support for our animal findings. Our results indicate that the COOH in PAA is involved in lung inflammation and fibrosis through specific changes in gene expression.