Effects of RNA interference-induced Smad3 gene silencing on pulmonary fibrosis caused by paraquat in mice.

Abstract

Paraquat (PQ) poisoning induces many physiological and histological changes in the human body, but PQ-induced pulmonary fibrosis is most often associated with death. The signaling pathway associated with pulmonary fibrosis is reliant on transforming growth factor-beta 1 (tgf-β(1)) activation of Smad3, as evidenced by Smad3-deficient mice being resistant to tgf-β(1)-induced pulmonary fibrosis. Thus, we sought to determine whether targeted silencing of Smad3 gene expression could inhibit PQ-induced pulmonary fibrosis in mice. We developed an RNA interference (RNAi) method using short hairpin RNAs (shRNAs) targeting Smad3. The shRNA expression cassettes capable of effectively silencing Smad3 in L929 mouse fibroblasts were transferred to an adenovirus vector and intratracheally administered into mouse lung. Treated mice presented with inhibited Smad3 mRNA and protein and were resistant to PQ-induced pulmonary fibrosis, as evidenced by suppressed expressions of procollagen type I mRNA and hydroxyproline amino acid. Thus, silencing of Smad3 appears to be a promising alternative strategy for the treatment of PQ-induced pulmonary fibrosis.

• Authors: Xue-Song Dong, Xiao-Bin Hu, Wei Liu, Yu-Qiang Sun, Zhi Liu
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 237 Issue 5 Pg. 548-55 (May 2012) ISSN: 1535-3699 [Electronic] England
• PMID: 22581813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• RNA, Messenger
• RNA, Small Interfering
• Smad3 Protein
• Smad3 protein, mouse
• Transforming Growth Factor beta1
• Paraquat

Topics

• Animals
• Collagen Type I (biosynthesis, genetics)
• Lung (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Paraquat (pharmacology, poisoning)
• Pulmonary Fibrosis (chemically induced, genetics, pathology, therapy)
• RNA Interference
• RNA, Messenger (biosynthesis)
• RNA, Small Interfering
• Signal Transduction (genetics)
• Smad3 Protein (genetics, physiology)
• Transforming Growth Factor beta1 (biosynthesis, genetics)