LncRNA gm40262 promotes liver fibrosis and parasite growth through the gm40262-miR-193b-5p-TLR4/Col1α1 axis
Tingli Liu,
Guiting Pu,
Liqun Wang,
Ziyu Ye,
Hong Li,
Rui Li,
Yanping Li,
Xiaola Guo,
William C. Cho,
Hong Yin,
Yadong Zheng,
Xuenong Luo
Affiliations
Tingli Liu
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Guiting Pu
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Liqun Wang
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Ziyu Ye
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang province, China
Hong Li
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Rui Li
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang province, China
Yanping Li
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Xiaola Guo
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
William C. Cho
Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong, China
Hong Yin
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
Yadong Zheng
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, Zhejiang province, China
Xuenong Luo
State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu Province, China
ABSTRACT Alveolar echinococcosis (AE) is a severe and life-threatening parasitic disease caused by Echinococcus multilocularis. Liver fibrosis is a significant pathological feature of advanced AE, characterized by the excessive production and accumulation of extracellular matrix (ECM). However, the precise underlying mechanism remains largely unknown. In this study, we show that the long noncoding RNA gm40262, predominantly expressed in hepatic stellate cells (HSCs), is upregulated in AE. Interestingly, its knockdown leads to liver fibrosis resolution, accompanied by a substantial suppression of parasite growth. Gm40262 functions by targeting miR-193b-5p to activate HSCs and stimulate their proliferation in a TGF-β-dependent manner, thereby promoting ECM production by upregulating Col1α1. Moreover, gm40262 is also involved in inflammation through the gm40262-miR-193b-5p-TLR4 axis. Our findings suggest that gm40262 plays a pivotal role in parasite-induced liver fibrosis through multiple mechanisms, highlighting its potential as a therapeutic target for hepatic fibrosis.IMPORTANCEEchinococcus multilocularis is a tiny parasite with significant medical implications. The chronic parasitism of E. multilocularis in the liver generally leads to liver fibrosis, but the underlying mechanisms are poorly understood. We herein show that gm40262, a long noncoding RNA predominantly expressed in hepatic stellate cells (HSCs), is involved in hepatic fibrogenesis during infection by activating HSCs and promoting extracellular matrix production. The gm40262-orchestrating fibrogenesis occurs through the gm40262-miR-193b-5p-TLR4 and gm40262-miR-193b-5p-Col1α1 axes. The knockdown of gm40262 remarkably alleviates liver fibrosis, with decreased parasite growth. Our findings reveal a key role of gm40262 in liver fibrosis during E. multilocularis infection, rendering it a therapeutic target for hepatic fibrosis.
