Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress

Zhang, Lei1; Zeng, Jieying2; Wu, Huaiyu2; Tian, Hongtian2; Song, Di2; Wu, Weiqing1; Dong, Fajin2,3,4

2023-12-01

10.1016/j.amjms.2023.08.016

AMERICAN JOURNAL OF THE MEDICAL SCIENCES   影响因子和分区

0002-9629

1538-2990

Background: Hepatic fibrosis is a common pathological process in many chronic liver diseases. TXNDC5 has been shown to be involved in the progression of renal and pulmonary fibrosis. However, the role of TXNDC5 in hepatic fibrosis is unknown. The purpose of this study is to explore the role and mechanism of TXNDC5 in hepatic fibrosis.Methods: We used TGF-(31 to activate LX-2 cells and reduced TXNDC5 expression by short hairpin RNA. Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry or Tunel assay. The fibrosis-related proteins and endoplasmic reticulum stress (ERs)-related proteins were measured by western blot. ELISA was performed to detect COL1AL levels and MMP2/9 activities in cell medium. A mouse model of hepatic fibrosis was constructed by intraperitoneal injection of CCL4. HE and Masson staining were performed to assess fibrosis in mouse liver tissue. Results: The results show that TXNDC5 was up-regulated in activated LX-2 cells and CCL4-induced hepatic fibrosis mice. Knockdown of TXNDC5 inhibited the viability of activated LX-2 cells and the production of collagen COL1A1. Knockdown of TXNDC5 promoted apoptosis of activated LX-2 cells. Mechanically, inhibition of TXNDC5 enhanced ERs, and the ERs inhibi-tor 4-Phenylbutyric acid (4-PBA) reversed the effect of TXNDC5 on activated LX-2 cells. More importantly, knockdown of TXNDC5 alleviated CCl4-induced hepatic fibrosis in mice.Conclusions: Knockdown of TXNDC5 may reduce hepatic fibrosis by regulating ERs, and targeting TXNDC5 seems to be a candidate treatment for hepatic fibrosis.

TXNDC5 Hepatic fibrosis Hepatic stellate cell Endoplasmic reticulum stress

SCI

英语

第一 ; 通讯

Commission of Science and Technology of Shenzhen[GJHZ20200731095401004]

General & Internal Medicine

Medicine, General & Internal

WOS:001108330000001

ELSEVIER SCIENCE INC

CLINICAL MEDICINE

Web of Science

1.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Hlth Manage, Shenzhen, Guangdong, Peoples R China
2.Jinan Univ, Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1,Clin Med Coll 2,Dept Ultrasound, Shenzhen, Guangdong, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, 1017 East gate Rd, Shenzhen 518020, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China

Zhang, Lei,Zeng, Jieying,Wu, Huaiyu,et al. Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress[J]. AMERICAN JOURNAL OF THE MEDICAL SCIENCES,2023,366(6).

Zhang, Lei.,Zeng, Jieying.,Wu, Huaiyu.,Tian, Hongtian.,Song, Di.,...&Dong, Fajin.(2023).Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress.AMERICAN JOURNAL OF THE MEDICAL SCIENCES,366(6).

Zhang, Lei,et al."Knockdown of TXNDC5 alleviates CCL4-induced hepatic fibrosis in mice by enhancing endoplasmic reticulum stress".AMERICAN JOURNAL OF THE MEDICAL SCIENCES 366.6(2023).