[Emodin alleviates pulmonary fibrosis through inactivation of TGF-β1/ADAMTS-1 signaling pathway in rats].
Objective To explore the role of transforming growth factor-β1 (TGF-β1)/a disintegrin-like and metalloproteinase with thrombospondin type 1 motif (ADAMTS-1) signaling pathway in emodin's anti-pulmonary fibrosis. Methods Sixty SD rats were randomly divided into 6 groups: normal control group, sham-operated group, model group, low-dose emodin intervention group (20 mg/kg), high-dose emodin intervention group (80 mg/kg) and prednisone group (5 mg/kg). Each group included 10 animals. Rats in the latter 4 groups were intratracheally injected with bleomycin A5 to induce pulmonary fibrosis, whereas bleomycin A5 was replaced by normal saline in sham-operated group. From the second day, rats in the low- and high-dose emodin intervention groups were intragastrically treated with 2 mL of 20 and 80 mg/kg emodin, respectively. Rats in the prednisone group were intragastrically administrated with 2 mL of 5 mg/kg prednisone acetate. However, rats in the normal control and sham-operated and model groups were treated with 2 mL of normal saline. All rats were sacrificed on day 28 after modeling. Subsequently, blood and pulmonary tissue specimen were taken. The pathological changes of pulmonary tissues were observed using routine HE and Masson staining. The expressions of TGF-β1, ADAMTS-1, collagen type 1 (Col1) and Col3 in pulmonary tissues were measured by quantitative real-time PCR and Western blotting. Serum levels of procollagen type 1 carboxy terminal propeptide (P1CP) and procollagen type 3 aminoterminal propeptide (P3NP) were detected by ELISA. Results Compare with the model group, the alveolitis and pulmonary fibrosis extent in each drug-treated group were significantly alleviated. In comparison with normal control group or sham-operated group, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP increased, but the mRNA and protein levels of ADAMTS-1 decreased in model group. After treatment with low- and high-dose emodin or prednisone, the mRNA and protein levels of TGF-β1, Col1 and Col3 in pulmonary tissues and the serum levels of P1CP and P3NP were significantly downregulated, while the mRNA and protein levels of ADAMTS-1 in pulmonary tissues were significantly upregulated as compared with the model group. Moreover, In comparison with the low-dose emodin intervention group, the above indicators were significantly improved in the high-dose emodin intervention or prednisone group. However, the above indicators were not significantly different between the high-dose emodin intervention group and the prednisone group. Conclusion Increased degradation of Col1 and Col3 in pulmonary tissues due to the inactivation of TGF-β1/ADAMTS-1 signaling pathway may be a significant mechanism by which emodin protects rats against pulmonary fibrosis.
School of Clinical Medicine, Hunan University of Medicine, Huaihua 418000, China.
Lijing
L
Liu
School of Clinical Medicine, Hunan University of Medicine, Huaihua 418000, China.
Hong
H
Qian
Department of Respiration, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Hua
H
Xiao
Department of Respiration, Huaihua First People's Hospital, Huaihua 418000, China. *Corresponding author, E-mail: hjb0919@aliyun.com.
Jianbin
J
He
Department of Respiration, Huaihua First People's Hospital, Huaihua 418000, China.
Maofeng
M
Xie
Department of Respiration, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Zaiyan
Z
Wang
Department of Respiration, First Affiliated Hospital, University of South China, Hengyang 421001, China.
Xingyun
X
Long
D000071097:ADAMTS1 Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004642:Emodin / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
D024042:Collagen Type I; D024061:Collagen Type III; D004365:Drugs, Chinese Herbal; D010446:Peptide Fragments; D011347:Procollagen; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D000071097:ADAMTS1 Protein; C486324:Adamts1 protein, rat; D004642:Emodin