Umbilical cord mesenchymal stem cell alleviates asthma via Nrf2/HO-1/NF-κB signaling pathway

Abstract

Background Numerous previous studies have proved the immunomodulatory properties of mesenchymal stem cells (MSCs) especially for human umbilical cord mesenchymal stem cells (UC.MSCs) in the progression of asthma, but the action mechanism remains unclear.Methods In the present work, a rat asthma model induced by ovalbumin (OVA) was established to ascertain the effects of UC.MSCs treatment on inflammation, oxidative stress and airway remodeling. Additionally, both in rat asthma model and TGF-β-induced airway smooth muscle cells (ASMCs), the interaction of UC.MSCs with Nrf2/HO-1/NF-κB pathway was evaluated.Results We demonstrated that OVA-induced inflammation infiltration and the increase of cell counts of eosinophils, lymphocytes, and macrophages were dramatically reduced after UC.MSCs treatment. The downregulated expression of anti-oxidant genes (NQO1 and HO-1), and the reduced GSH levels caused by OVA challenge were restored following the treatment of UC.MSCs. Meanwhile, UC.MSCs also prohibited collagen deposition, suppressed goblet cell hyperplasia and decreased the levels of airway remodeling markers (α-SMA, TGF-β1, MMP9 and TIMP1) in asthma rat model. In in vitro experiments, TGF-β could facilitate the viability of ASMCs and restrain G1 cell cycle arrest, while UC.MSCs revised these changes. Additionally, treatment with UC.MSCs could significantly activate the expression of HO-1 and NRF2, but inhibit NF-κB levels in vivo and in vitro.Conclusions In a word, these findings indicated that UC.MSCs can alleviate asthma via Nrf2/HO-1/NF-κB signaling pathway, which provided a theoretical basis for asthma therapy in clinic.