Huangqi Decoction, a compound Chinese herbal medicine, inhibits the proliferation and activation of hepatic stellate cells by regulating the long noncoding RNA-C18orf26-1/microRNA-663a/transforming growth factor-ß axis.

OBJECTIVE: Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-ß/small mothers against decapentaplegic (TGF-ß/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-ß/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis. METHODS: The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-ß/Smad signaling pathway-related proteins were determined using Western blotting. RESULTS: Lnc-C18orf26-1 was upregulated in TGF-ß1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-ß1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-ß1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-ß1, TGF-ß type I receptor (TGF-ßRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment. CONCLUSION: Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-ß1/TGF-ßRI/p-Smad2 axis.

[Distribution and significance of IgG subclasses of serum antithyroglobulin antibody in Hashimoto thyroiditis].

OBJECTIVE: To evaluate the distribution and significance of IgG subclasses of antithyroglobulin antibody in sera from patients with Hashimoto thyroiditis. METHODS: Sera from 112 patients with Hashimoto thyroiditis were collected and patients were divided into 3 groups, i. e. hypothyroidism, subclinical hypothyroidism and euthyroidism. Antigen specific ELISA was used to detect the distribution of IgG subclasses of antithyroglobulin antibody. RESULTS: The positive rates of IgG subclasses of TgAb were IgG1 90.2%, IgG2 58.0%, IgG3 19.6% and IgG4 87.5% respectively. The mean geometric titers of IgG1 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1: 450.8 and 1: 245.5 respectively, both being significantly higher than that with euthyroidism (1:8.7, P < 0.01). The mean geometric titers of IgG2 in sera from patients with hypothyroidism and subclinical hypothyroidism were 1: 37.3 and 1: 3.2 respectively, both being also significantly higher than that with euthyroidism (1: 0.2, P < 0.01 and P < 0.05 respectively) and that with hypothyroidism was significantly higher than that with subclinical hypothyroidism (P < 0.05). CONCLUSION: The distribution of IgG subclasses of antithyroglobulin antibody in sera from patients with Hashimoto thyroiditis was predominantly IgG1, IgG2 and IgG4. High titers of IgG1 and IgG2 implicated the possibility of development from subclinical hypothyroidism to overt hypothyroidism.