Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats
Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1149665/full |
| _version_ | 1797810604079054848 |
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| author | Shengpeng Zhang Peng Zhu Jianan Yuan Kunming Cheng Qixiang Xu Wei Chen Zui Pan Yongqiu Zheng |
| author_facet | Shengpeng Zhang Peng Zhu Jianan Yuan Kunming Cheng Qixiang Xu Wei Chen Zui Pan Yongqiu Zheng |
| author_sort | Shengpeng Zhang |
| collection | DOAJ |
| description | Rheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection of Freund’s complete adjuvant (FCA) with bovine type II collagen. Collagen-induced RA (CIA) was confirmed by hind paw swelling and histological examination. The histomorphological characteristics of NAFLD were evaluated by Masson’s trichrome and hematoxylin-eosin staining. The development of NAFLD was further evaluated by measuring serum concentrations of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipopolysaccharide (LPS). The results showed that HFD feeding exacerbated secondary inflammation in CIA rats, whereas FCA/bovine type II collagen injection increased serum levels of ALT, AST, TG, T-CHO, and LPS and exacerbated hepatic fibrosis in both normal and NAFLD rats. Interestingly, NAFLD + CIA significantly promoted the expression of PTRF, a caveolae structure protein involved in hepatic lipid metabolism and affecting downstream signaling of Toll-like receptor 4 (TLR4) and PI3K/Akt activation. High resolution confocal microscopy revealed increased PTRF and TLR4 co-localization in hepatic small vessels of NAFLD + CIA rats. AAV9-mediated PTRF knockdown inhibited TLR4 signaling and alleviated hepatic fibrosis in NAFLD + CIA rats. Together, these findings indicate that NAFLD combined with CIA causes synovial injury and enhances non-alcoholic fatty liver fibrosis in rats. PTRF could attenuate the symptoms of NAFLD + CIA likely by affecting TLR4/PTRF co-expression and downstream signaling. |
| first_indexed | 2024-03-13T07:10:14Z |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-13T07:10:14Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-e4a913b7f2ae494ebbc6ff70743b96d32023-06-06T04:35:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.11496651149665Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in ratsShengpeng Zhang0Peng Zhu1Jianan Yuan2Kunming Cheng3Qixiang Xu4Wei Chen5Zui Pan6Yongqiu Zheng7School of Pharmacy, Wannan Medical College, Wuhu, ChinaSchool of Pharmacy, Wannan Medical College, Wuhu, ChinaSchool of Pharmacy, Wannan Medical College, Wuhu, ChinaSchool of Pharmacy, Wannan Medical College, Wuhu, ChinaSchool of Pharmacy, Wannan Medical College, Wuhu, ChinaBoster Biological Technology Co., Ltd., Wuhan, ChinaCollege of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, TX, United StatesSchool of Pharmacy, Wannan Medical College, Wuhu, ChinaRheumatoid arthritis (RA) has a high prevalence in patients with non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. To address this, our study established a rat model with both NAFLD and RA by feeding a high-fat diet (HFD) and administering intradermal injection of Freund’s complete adjuvant (FCA) with bovine type II collagen. Collagen-induced RA (CIA) was confirmed by hind paw swelling and histological examination. The histomorphological characteristics of NAFLD were evaluated by Masson’s trichrome and hematoxylin-eosin staining. The development of NAFLD was further evaluated by measuring serum concentrations of triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipopolysaccharide (LPS). The results showed that HFD feeding exacerbated secondary inflammation in CIA rats, whereas FCA/bovine type II collagen injection increased serum levels of ALT, AST, TG, T-CHO, and LPS and exacerbated hepatic fibrosis in both normal and NAFLD rats. Interestingly, NAFLD + CIA significantly promoted the expression of PTRF, a caveolae structure protein involved in hepatic lipid metabolism and affecting downstream signaling of Toll-like receptor 4 (TLR4) and PI3K/Akt activation. High resolution confocal microscopy revealed increased PTRF and TLR4 co-localization in hepatic small vessels of NAFLD + CIA rats. AAV9-mediated PTRF knockdown inhibited TLR4 signaling and alleviated hepatic fibrosis in NAFLD + CIA rats. Together, these findings indicate that NAFLD combined with CIA causes synovial injury and enhances non-alcoholic fatty liver fibrosis in rats. PTRF could attenuate the symptoms of NAFLD + CIA likely by affecting TLR4/PTRF co-expression and downstream signaling.https://www.frontiersin.org/articles/10.3389/fphar.2023.1149665/fullnon-alcoholic fatty liver diseaserheumatoid arthritispolymerase I and transcript release factorTLR4PTRFPI3K/AKT signaling |
| spellingShingle | Shengpeng Zhang Peng Zhu Jianan Yuan Kunming Cheng Qixiang Xu Wei Chen Zui Pan Yongqiu Zheng Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats Frontiers in Pharmacology non-alcoholic fatty liver disease rheumatoid arthritis polymerase I and transcript release factor TLR4 PTRF PI3K/AKT signaling |
| title | Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats |
| title_full | Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats |
| title_fullStr | Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats |
| title_full_unstemmed | Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats |
| title_short | Non-alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co-localization of PTRF and TLR4 in rats |
| title_sort | non alcoholic fatty liver disease combined with rheumatoid arthritis exacerbates liver fibrosis by stimulating co localization of ptrf and tlr4 in rats |
| topic | non-alcoholic fatty liver disease rheumatoid arthritis polymerase I and transcript release factor TLR4 PTRF PI3K/AKT signaling |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1149665/full |
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