Ppic modulates CCl4-induced liver fibrosis and TGF-β-caused mouse hepatic stellate cell activation and regulated by miR-137-3p

Yang, Xin; Shu, Bo; Zhou, Yingxia; Li, Zhuan; He, Chao

doi:10.1016/j.toxlet.2021.06.021

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…PPIC is associated with protein folding and is upregulated in CCL4-induced liver injury. PPIC loss of function was shown to improve liver injury, suggesting it may be involved in fibrosis progression ( 70 ). Similarly, ALDH3B1 , which is involved in oxidative stress, is highly expressed in lung cancer ( 71 ).…”

Section: Resultsmentioning

confidence: 99%

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Herrera¹,

Dingle²,

Fernandez³

et al. 2022

JCI Insight

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Usual Interstitial Pneumonia (UIP) is a histological pattern characteristic of Idiopathic Pulmonary Fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subject to qualitative and quantitative analysis, and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared to non-fibrotic control. Furthermore, the FF is positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of the FF is predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that the FF is the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This new and essential information will inform future mechanistic studies on fibrosis progression.

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Section: Resultsmentioning

confidence: 99%

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Herrera¹,

Dingle²,

Fernandez³

et al. 2022

JCI Insight

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“…This is relevant, as PPIC encodes for an isomerase that seems to be implicated in protein folding. Interestingly, this gene is reported to play an important role in the differentiation of B lymphocytes and invariant NK T cells [49], as well as in hepatic fibrosis, as its knockdown in a CCl 4 ‐induced mouse model and in TGF‐β‐activated HSC was shown to attenuate fibrosis and reduce extracellular matrix deposition [50]. Together, this evidence encourages a better understanding of its role in hepatocytes and its implication in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Integrated transcriptomic landscape of the effect of anti‐steatotic treatments in high‐fat diet mouse models of non‐alcoholic fatty liver disease

Fuster‐Martínez,

Català‐Senent,

Hidalgo

et al. 2024

The Journal of Pathology

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High‐fat diet (HFD) mouse models are widely used in research to develop medications to treat non‐alcoholic fatty liver disease (NAFLD), as they mimic the steatosis, inflammation, and hepatic fibrosis typically found in this complex human disease. The aims of this study were to identify a complete transcriptomic signature of these mouse models and to characterize the transcriptional impact exerted by different experimental anti‐steatotic treatments. For this reason, we conducted a systematic review and meta‐analysis of liver transcriptomic studies performed in HFD‐fed C57BL/6J mice, comparing them with control mice and HFD‐fed mice receiving potential anti‐steatotic treatments. Analyzing 21 studies broaching 24 different treatments, we obtained a robust HFD transcriptomic signature that included 2,670 differentially expressed genes and 2,567 modified gene ontology biological processes. Treated HFD mice generally showed a reversion of this HFD signature, although the extent varied depending on the treatment. The biological processes most frequently reversed were those related to lipid metabolism, response to stress, and immune system, whereas processes related to nitrogen compound metabolism were generally not reversed. When comparing this HFD signature with a signature of human NAFLD progression, we identified 62 genes that were common to both; 10 belonged to the group that were reversed by treatments. Altered expression of most of these 10 genes was confirmed in vitro in hepatocytes and hepatic stellate cells exposed to a lipotoxic or a profibrogenic stimulus, respectively. In conclusion, this study provides a vast amount of information about transcriptomic changes induced during the progression and regression of NAFLD and identifies some relevant targets. Our results may help in the assessment of treatment efficacy, the discovery of unmet therapeutic targets, and the search for novel biomarkers. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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“…Findings from Wei et al identified AFM as a potential target of miR-137-3p to mediate its regulation on the progression of hepatocellular carcinoma [ 24 ]. More recently, Yang et al reported that miR-137-3p negatively regulated peptidylprolyl isomerase C (Ppic) expression via direct targeting and that Ppic knockdown partially reversed the effects of miR-137-3p inhibition [ 57 ]. Whether other possible targets of miR-137-3p exist in the regulation of NAFLD remains unclear and needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

Sheng

et al. 2021

Analytical Cellular Pathology

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Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and can develop to nonalcoholic steatohepatitis and later hepatic cirrhosis with a high prevalence to hepatocellular carcinoma. Oxidative stress and chronic hepatic inflammation are implicated in the pathogenesis of NAFLD. MicroRNA-137-3p (miR-137-3p) are associated with oxidative stress and inflammation; however, its role and mechanism in NAFLD remain unclear. Mice were fed with a high-fat diet (HFD) for 24 weeks to establish the NAFLD model. To overexpress or suppress hepatic miR-137-3p expression, mice were intraperitoneally injected with the agomir, antagomir, or respective controls of miR-137-3p at a dose of 100 mg/kg weekly for 6 consecutive weeks before the mice were sacrificed. To validate the involvement of AMP-activated protein kinase alpha (AMPKα) or cAMP-specific phosphodiesterase 4D (PDE4D), HFD mice were intraperitoneally injected with 20 mg/kg compound C or 0.5 mg/kg rolipram every other day for 8 consecutive weeks before the mice were sacrificed. Hepatic miR-137-3p expression was significantly decreased in mice upon HFD stimulation. miR-137-3p agomir alleviated, while miR-137-3p antagomir facilitated HFD-induced oxidative stress, inflammation, and hepatic dysfunction in mice. Mechanistically, we revealed that miR-137-3p is directly bound to the 3 ′ -untranslated region of PDE4D and subsequently increased hepatic cAMP level and protein kinase A activity, thereby activating the downstream AMPKα pathway. In summary, miR-137-3p improves NAFLD through activating AMPKα and it is a promising therapeutic candidate to treat NAFLD.

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Ppic modulates CCl4-induced liver fibrosis and TGF-β-caused mouse hepatic stellate cell activation and regulated by miR-137-3p

Cited by 7 publications

References 40 publications

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix

Integrated transcriptomic landscape of the effect of anti‐steatotic treatments in high‐fat diet mouse models of non‐alcoholic fatty liver disease

MicroRNA-137-3p Improves Nonalcoholic Fatty Liver Disease through Activating AMPKα

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