Adipokines, secreted by the adipose tissue, are extensively involved in the regulation and maintenance of various physiological and pathological processes, including insulin sensitivity, energy expenditure, glucose and lipid metabolism, inflammatory activity, neuroendocrine activity, immunity, cancer, homeostasis, angiogenesis, cardiovascular function, breeding and bone metabolism, and all functions of the endocrine-reproductive system axis. Omentin is a recently identified adipokine, which has become a research hotspot due to its pleiotropic effects on various diseases. However, the specific receptor for omentin has not been identified so far. In this study, we report that omentin levels fluctuate in various diseases. In addition, we have focused on the pleiotropic roles of omentin in pulmonary diseases, as it may act as a biomarker for malignant pleural mesothelioma (MPM) and is related to disease severity. Omentin may play significant roles in other pulmonary diseases, such as asthma, obstructive sleep apnea syndrome (OSAS), pulmonary arterial hypertension (PAH), acute respiratory distress syndrome (ARDS), and chronic obstructive pulmonary disease (COPD). This review summarizes the advances in current knowledge and future trends, which may provide a concise and general view on omentin and its effects on pulmonary biology.
Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc− in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-β1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.
Acute lung injury (ALI) is a severe health issue with significant morbidity and mortality. Artemisinin is used for the treatment of fever and malaria in clinical practice. Dihydroartemisinin (DHA), the major active metabolite of artemisinin, plays a role in anti-organizational fibrosis and anti-neuronal cell death. However, whether DHA can attenuate ALI remains unclear. The current study thus examined the effects of DHA on ALI and primary macrophages. The results revealed that DHA attenuated lipopolysaccharide (LPS)-induced pulmonary pathological damage. DHA suppressed the LPS-induced infiltration of inflammatory cells, the elevation of myeloperoxidase activity, oxidative stress and the production of pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α, and IL-6. Furthermore, DHA reduced the LPS-induced inflammatory response by suppressing the degradation of I-κB and the nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)/p65 in vivo and in vitro. DHA activated the nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway, which was suppressed by LPS treatment. The Nrf2 inhibitor, ML385, diminished the protective effects of DHA against LPS-induced inflammation in macrophages. On the whole, the findings of this study demonstrate that DHA exerts therapeutic effects against LPS-induced ALI by inhibiting the Nrf2-mediated NF-κB activation in macrophages. The present study also confirmed the therapeutic effects of DHA in mice with LPS-induced ALI. Thus, these findings demonstrate that DHA exhibits anti-inflammatory activities and may be a therapeutic candidate for the treatment of ALI.
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