HMGB1 induces lung fibroblast to myofibroblast differentiation through NF-κB-mediated TGF-β1 release

Wang, Qiong; Wang, Jun; Wang, Junfang; Hong, Shanchao; Han, Feifei; Chen, Jingyu; Guo-qian, Chen

doi:10.3892/mmr.2017.6364

Cited by 48 publications

(34 citation statements)

References 39 publications

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“…In addition, several studies have reported that NF-κB can directly regulate the expression and secretion of TGF-β1. For example, NF-κB can promote the release of TGF-β1 in pulmonary fibrosis [45], whereas inhibition of the TLR4/MyD88/NF-κB pathway can downregulate the expression of TGF-β1 in glomerular mesangial cells [46]. A similar phenomenon was also observed in myocardia, where the activation of NF-κB can lead to an increase in the expression of its downstream target gene TGF-β1 [47].…”

Section: Discussionmentioning

confidence: 78%

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Jiang

Zhou

Hou

et al. 2019

The Journal of Pathology

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Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT‐qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient‐derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial–mesenchymal transition (EMT)‐like processes in vivo and in vitro. Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT‐like processes via the TGF‐β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

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Section: Discussionmentioning

confidence: 78%

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Jiang

Zhou

Hou

et al. 2019

The Journal of Pathology

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“…The important role of HMGB1 in fibroblast activation has been explored in vitro. Studies have shown that HMGB1 can induce fibroblasts to differentiate into myofibroblasts (Wang et al, 2017), an essential process that is responsible for excessive extracellular matrix deposition and tissue contraction during hypertrophic scar formation. Therefore, these data prompted us to investigate the role of HMGB1 in scar development, which is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Epidermal HMGB1 Activates Dermal Fibroblasts and Causes Hypertrophic Scar Formation in Reduced Hydration

Zhao

et al. 2018

Journal of Investigative Dermatology

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HMGB1 protein is a multifunctional cytokine involved in inflammatory reactions and is known to play a key role in tissue repair and fibrosis. However, the function of HMGB1 in fibrotic skin diseases, such as hypertrophic scar formation, remains unclear. In this study, HMGB1 was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, we found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts. HMGB1 secreted from keratinocytes activated fibroblasts by promoting the nuclear import of MRTF-A, increased the nuclear accumulation of MRTF-A/SRF complexes and consequently enhanced α-smooth muscle actin promoter activation. Moreover, blockade of advanced glycation end products or Toll-like receptor 2/4 inhibited the fibroblast activation induced by HMGB1. Finally, local delivery of HMGB1 resulted in marked hypertrophic scar formation in rabbit hypertrophic scar models, while HMGB1 blockade exerted a clear anti-scarring effect. Our results indicate that high HMGB1 levels induced by a reduced hydration status play an important role in hypertrophic scar formation, strongly suggesting that HMGB1 is a novel target for preventing scarring.

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“…HMGB1 exerts its effect in different diseases through the RAGE/NF‐κB signaling pathway; in addition, HMGB1 stimulation increased the activation of NF‐κB and the release of TGF‐β1, as well as α‐SMA and collagen I expression in human lung fibroblasts in vitro . To investigate the mechanism by which miR‐627/HMGB1 modulates TGF‐β1‐induced PF in vitro, we further explored whether miR‐627/HMGB1 could affect TGF‐β1 release through RAGE/NF‐κB signaling in NHLFs.…”

Section: Discussionmentioning

confidence: 99%

miR‐627/HMGB1/NF‐κB regulatory loop modulates TGF‐β1‐induced pulmonary fibrosis

Kong

Jiang

et al. 2018

J of Cellular Biochemistry

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Pulmonary fibrosis (PF) is a fibroproliferative disease that can eventually lead to fatal lung failure. It is characterized by abnormal proliferation of fibroblasts, dysregulated fibroblast differentiation to myofibroblast, and disorganized collagen and extracellular matrix production, deposition and degradation.There is still a lack of effective treatment strategies for PF. Extracellular highmobility group box protein 1 (HMGB1) induces PF through NF-κB-mediated TGF-β1 release. Herein, we first validate the suppressive effect of HMGB1 knockdown on TGF-β1-induced α-smooth muscle actin (α-SMA) and collagen I protein expression. In PF, miRNAs exert different effects through targeting various downstream target messenger RNAs. We searched an online database for dysregulated miRNAs in PF tissues; among them, miR-627 was predicted by online tools to target HMGB1 to inhibit its expression. miR-627 overexpression could partially reverse TGF-β1-induced normal human lung fibroblast proliferation, as well as α-SMA and collagen I protein expression. miR-627 inhibition could partially reverse the suppressive effect of HMGB1 knockdown on TGF-β1-induced α-SMA and collagen I protein expression through direct binding to the 3′-untranslated region of HMGB1. Moreover, miR-627/HMGB1

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HMGB1 induces lung fibroblast to myofibroblast differentiation through NF-κB-mediated TGF-β1 release

Cited by 48 publications

References 39 publications

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Epidermal HMGB1 Activates Dermal Fibroblasts and Causes Hypertrophic Scar Formation in Reduced Hydration

miR‐627/HMGB1/NF‐κB regulatory loop modulates TGF‐β1‐induced pulmonary fibrosis

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