{'fraction_non_alphanumeric': 0.03776325344952796, 'fraction_numerical': 0.021060275962236745, 'mean_word_length': 5.754901960784314, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
IL-22 inactivates hepatic stellate cells via downregulation of the TGF-β1/Notch signaling pathway.

Interleukin-22 (IL-22) inhibits liver fibrosis by inducing hepatic stellate cell (HSC) senescence, primarily through the activation of signal transducer and activator of transcription 3 signaling. However, whether other signaling pathways are involved remains unknown. The present study assessed the regulatory mechanism between IL‑22 and the Notch signaling pathway in vitro. The results revealed that IL‑22 had anti‑proliferative effects on HSC‑T6 cells, and cellular inactivation was reflected by simultaneous inhibition of α‑smooth muscle actin, transforming growth factor-β1 (TGF‑β1), tumor necrosis factor-α and intercellular adhesion molecule 1. Treatment with TGF‑β1 resulted in significant Notch3 upregulation and activation of its downstream effectors Hes family basic helix‑loop‑helix (bHLH) transcription factor (Hes)-1, Hes‑5 and Hes related family BHLH transcription factor with YRPW motif 1. Furthermore, this effect was markedly reversed by further treatment with IL‑22, indicating there may be regulatory cascades of IL‑22/TGF‑β1/Notch signaling in HSC‑T6 cells. The results of the present study demonstrated an inhibitory function of IL‑22 towards Notch signaling in hepatic cells, providing evidence that Notch may serve as a novel target for liver fibrosis.