Target identification of hepatic fibrosis using Pien Tze Huang based on mRNA and lncRNA

Jinhang Zhu,Jing Sun,Ting Wang,Muyun Wei,Hao Wu,Luan Chen,Na Zhang,Di Zhang,Fei Hong,Zhiliang Chen,Shengying Qin,Cong Huai

doi:10.1038/s41598-021-96459-5

Jinhang Zhu, Jing Sun + Show 10 more

Open Access

https://doi.org/10.1038/s41598-021-96459-5

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Abstract

Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We used a CCl4-induced mouse model to establish a PZH group of hepatic fibrosis mice treated with PZH and a control group of hepatic fibrosis mice without any treatment. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Liver functional indices, including serum albumin (ALB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were significantly decreased in the PZH treatment group (P < 0.05) in the eighth week. Hematoxylin–eosin (HE), Masson and Sirius red staining demonstrated that PZH significantly inhibited infiltration of inflammatory cells and collagen deposition. A total of 928 transcripts and 138 proteins were differentially expressed in PZH-treated mice compared to the control group. Gene Ontology (GO) enrichment analysis suggested that PZH may alleviate liver injury and fibrosis by enhancing the immune process. Taken together, our results revealed that multiple DETs and DEPs may serve as drug targets of PZH in hepatic fibrosis patient in future clinical practice.

Highlights

Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury
These results demonstrated that Pien Tze Huang (PZH) treatment gradually alleviated the progression of hepatic fibrosis compared to the process observed in the control group
We performed the Sirius red staining and the results showed that the ratio of positive area of Sirius red staining accounting for total area was significantly decreased in PZH treatment group compared with non-treatment group (Fig. 2)

Summary

Introduction

Hepatic fibrosis is a spontaneous wound-healing response triggered by chronic liver injury. Pien Tze Huang (PZH), a traditional Chinese herbal medicine, has been widely used to treat various hepatic diseases in Asia. We performed RNA-seq and mass spectrometry sequencing to investigate the mechanism of the PZH response in hepatic fibrosis and identified multiple differentially expressed transcripts (DETs) and proteins (DEPs) that may be drug targets of PZH. Pien Tze Huang (PZH), a well-known herbal traditional Chinese medicine, is widely used in Asia for various liver diseases, including hepatic fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure[10,11]. Jinyan Zhao et al found that PZH ameliorates CCl4-induced liver injury, oxidative stress and inflammation in r ats[12]; Yang Yang et al found that PZH could ameliorate liver injury by inhibiting the PERK/ eIF2α signaling pathway in alcohol and high-fat diet r ats[13]; and Haiyin Zheng et al found that PZH ameliorates hepatic fibrosis by suppressing the NF-κB pathway using real-time PCR experiment methods based on rat and cell lines[14]. Analysis of mRNA and lncRNA expression is an important method to identify or explore their regulatory roles in the mechanisms of various d iseases[20,21,22]

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