Adiponectin inhibits the activation of lung fibroblasts and pulmonary fibrosis by regulating the nuclear factor kappa B (NF-κB) pathway

Abstract

Idiopathic pulmonary fibrosis (IPF) is a common pulmonary interstitial disease with a high mortality rate. Adiponectin (APN) is reportedly an effective therapy for fibrosis-related diseases. This study aimed to investigate the potential effects of APN on IPF. Male BALB/c mice were injected with bleomycin (BLM) and treated with different doses of APN (0.1, 0.25, and 0.5 mg/kg). The body weights of the mice were recorded. Immunohistochemical, hematoxylin and eosin, and Masson staining were performed to evaluate pulmonary histopathological changes. Enzyme-linked immunosorbent assay (ELISA) and western blotting were performed to assess tissue inflammation. The human lung fibroblasts HELF were stimulated with TGF-β1 and treated with different doses of APN (2.5, 5, and 10 μg/ml). Cell proliferation, inflammation, and fibrosis were determined by MTT assay, EdU assay, colony formation assay, ELISA, and western blotting. APN significantly attenuated BLM-induced body weight loss, alveolar destruction, and collagen fiber accumulation in mice ( p < 0.05). APN decreased the expression of α-SMA and collagen I and reduced the concentration of TNF-α, IL-6, IL-1β, and IL-18 in lung tissues ( p < 0.05). In TGF-β1-treated HELF cells, cell proliferation and colony formation were inhibited by APN ( p < 0.05). Additionally, the expression of α-SMA, collagen I, and pro-inflammatory cytokines were suppressed by APN ( p < 0.05). APN inhibited the phosphorylation of IκB and nuclear translocation of p65. In conclusion, these findings suggest that APN is an effective agent for controlling IPF progression. The antifibrotic effects of APN might be mediated via inhibiting the NF-κB signaling pathway.

Adiponectin Decreased Aquaporin 4 MRNA Expression in Rat Model of Type 1 Diabetic Retinopathy, Can It Prevent Retinal Edema?

“…Decreased serum IL-6 and TNF-α expression within the retinal tissue of adiponectin-treated diabetic retinopathy group goes in line with Wang et al [24] who found that adiponectin is effective in inhibiting inflammation, by inhibition of many cytokines (TNFα, IL-6, IL-1β, and IL-18) through inhibition of the NF-κB signaling inflammatory pathway. Adiponectin increases activity of anti-inflammatory factors e.g., IL-10.…”

The association between adipokines and pulmonary diseases: a mendelian randomization study

“…Nonetheless, experimental research has demonstrated that adiponectin can suppress the expression of alpha-smooth muscle actin (α-SMA), type I collagen, and pro-inflammatory cytokines [ 25 – 26 ]. Adiponectin has been proposed as a potential therapeutic agent for fibrosis-associated pathologies, its antifibrotic properties potentially mediated through the inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway [ 27 ]. Another study found that adiponectin mitigated paraquat-induced pulmonary fibrosis in a dose-responsive manner by inhibiting the activation of lung fibroblasts [ 28 ].…”

The mysterious association between adiponectin and endometriosis

“…The anti-fibrotic effects are mediated through the altered signaling of various pathways such as AMPK, PPAR, and TGF-β1/Smad, inhibiting the differentiation of fibroblasts to myofibroblasts and reducing the production as well as the deposition of extracellular matrix. Numerous studies have investigated its mechanism of action in fibrotic diseases of the kidneys (Jing et al, 2020;Zhao D. et al, 2021), liver (Dong et al, 2015;Udomsinprasert et al, 2018), heart (Fujita et al, 2008;Qi et al, 2014), lungs (Kökény et al, 2021;Wang et al, 2022), and skin (Wang et al, 2023), among other organs and systems, confirming its protective effects. Adiponectin was found to be capable of ameliorating tubulointerstitial fibrosis and suppressing angiotensin II-induced secretion of TGF-β1 and fibronectin in human renal mesangial cells, thereby reducing extracellular matrix synthesis (Tan et al, 2015).…”

“…Adiponectin was found to be capable of ameliorating tubulointerstitial fibrosis and suppressing angiotensin II-induced secretion of TGF-β1 and fibronectin in human renal mesangial cells, thereby reducing extracellular matrix synthesis ( Tan et al, 2015 ). Additionally, α-SMA expression was shown to be downregulated by adiponectin in the renal cortex of mice with progressive renal injury induced by the administration of deoxycorticosterone acetate and angiotensin II, as well as in the lung tissues of mice with bleomycin-induced idiopathic pulmonary fibrosis ( Tian et al, 2018 ; Wang et al, 2022 ). Another showed that the administration of the AdipoR agonists JT002, JT003, and JT004 significantly reduced the protein expression level of α-SMA in hepatic stellate cells and slowed the progression of hepatic fibrosis in mice ( Xu et al, 2020 ).…”