Correction: Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice.

[This corrects the article DOI: 10.18632/oncotarget.11225.].

Identification of Differentially Expressed Genes and Key Pathways in the Dorsal Root Ganglion After Chronic Compression.

Neuropathic pain (NP) is caused by primary or secondary impairment of the peripheral or central nervous systems. Its etiology is complex and involves abnormal patterns of gene expression and pathway activation. Using bioinformatics analysis, we aimed to identify NP-associated changes in genes and pathways in L4 and L5 dorsal root ganglia (DRG) in a rat model of NP induced by chronic compression of the DRG (CCD). Genome-wide transcriptional analyses were used to elucidate the molecular mechanisms underlying NP. We screened differentially expressed genes (DEGs) 7 days after CCD in comparison with sham-operated controls. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to confirm the presence of key DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathway analysis of DEGs and global signal transduction network analysis of DEGs were also conducted. The CCD group developed clear mechanical and thermal allodynia in the ipsilateral hind paw compared with the sham group. This comparison identified 1,887 DEGs, with 1156 upregulated and 731 downregulated DEGs, and 123 DEG-enriched pathways. We identified the key candidate genes that might play a role in the development of NP, namely syndecan 1 (Sdc1), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma (Pi3k), Janus kinase 2 (Jak2), jun proto-oncogene, AP-1 transcription factor subunit (Jun), and interleukin 6 (IL-6) by analyzing the global signal transduction network. RT-qPCR and western blot analysis confirmed the microarray results. The DEGs Sdc1, Pi3k, Jak2, Jun, and IL-6, and the cytokine signaling pathway, the neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway may have decisive modulatory roles in both nerve regeneration and NP. These results provide deeper insight into the mechanism underlying NP and promising therapeutic targets for its treatment.

Inhibition of Pin1 alleviates myocardial fibrosis and dysfunction in STZ-induced diabetic mice.

Therapeutic management of diabetic myocardial fibrosis remains an unsolved clinical problem. Pin1, a peptidyl-prolyl isomerase, impacts diverse cellular processes and plays a pivotal role in regulating cardiac pathophysiology. Here we investigate the potential mechanism of action of Pin1 and its role in diabetes-induced myocardial fibrosis and dysfunction in mice. Cardiac Pin1, transforming growth factor ß1 (TGF-ß1), α-smooth muscle actin (α-SMA) and extracellular matrix deposits (collagen I and III) are found to be increased in diabetic mice, which are effectively prevented by Pin1 inhibition by juglone. Pin1 inhibition alleviates cardiac fibrosis and dysfunction. In vitro, high glucose increases Pin1 expression with an accompanying increase in phospho-Akt (Ser 473), p-Smad2, p-Smad3, TGF-ß1, and α-SMA in cardiac fibroblasts (CFs). These increases are effectively prevented by the inhibition of Pin1 by juglone. Furthermore, Pin1 inhibition inhibits HG-induced CF proliferation and migration. Our results indicate that Pin1 inhibition attenuates cardiac extracellular matrix deposition by regulating the phosphorylation of Akt, TGF-ß1/Smads, MMP activities, and α-SMA expression in diabetic mice.

Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice.

Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Masson's trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-ß1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.