IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression

Tian, Tian; Xie, Rujia; Ding, Kaize; Han, Bing; Yang, Qin; Yang, Xue

doi:10.3892/etm.2021.9611

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…In relation to the effects of IOX-1 upon MMPs, previous research has reported that IOX-1 dosing of hepatic stellate cells signi cantly reduces levels of MMP1 expression by increasing H3K9me2 levels at the promoter region of MMP1 29 . Our study demonstrates that IOX-1 reduces levels of MMP2, MMP3, and MMP9 expression.…”

Section: Discussionmentioning

confidence: 99%

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

Li¹,

Lee

Yang

et al. 2022

Preprint

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New therapeutic approaches are needed for metastatic osteosarcoma (OS), as survival rates remain low despite surgery and chemotherapy. Epigenetic changes, such as histone H3 methylation, play key roles in many cancers including OS, although the underlying mechanisms are not clear. In this study, human OS tissue and OS cell lines displayed lower levels of histone H3 lysine trimethylation compared with normal bone tissue and osteoblast cells. Treating OS cells with the histone lysine demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX-1) dose-dependently increased histone H3 methylation and inhibited cellular migratory and invasive capabilities, suppressed matrix metalloproteinase expression, reversed epithelial-to-mesenchymal transition by increasing levels of epithelial markers E-cadherin and ZO-1 and decreasing the expression of mesenchymal markers N-cadherin, vimentin, and TWIST, and also reduced stemness properties. An analysis of cultivated MG63 cisplatin-resistant (MG63-CR) cells revealed lower histone H3 lysine trimethylation levels compared with levels in MG63 cells. Exposing MG63-CR cells to IOX-1 increased histone H3 trimethylation and ATP-binding cassette transporter expression, potentially sensitizing MG63-CR cells to cisplatin. In conclusion, our study suggests that histone H3 lysine trimethylation is associated with metastatic OS and that IOX-1 or other epigenetic modulators present promising strategies to inhibit metastatic OS progression.

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Section: Discussionmentioning

confidence: 99%

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

Li¹,

Lee

Yang

et al. 2022

Preprint

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show abstract

“…Previous studies have shown that overexpression of MMPs blocks the synthesis of skin collagen or elastin by disrupting ECM and promoting its cracking, leading to rough wrinkles and sagging skin and accelerating skin aging 26 . MMP‐1 can form a tight complex with TIMP‐1, and its activity can be specifically inhibited by TIMP‐1 and TIMP‐2 27 …”

Section: Discussionmentioning

confidence: 99%

“…26 MMP-1 can form a tight complex with TIMP-1, and its activity can be specifically inhibited by TIMP-1 and TIMP-2. 27 A TGFβ/Smad signaling pathway is a powerful activator of connective tissue synthesis and fibroblast proliferation, which physiologically and pathologically regulates fibroblast and collagen production and extracellular matrix renewal. 28 Firstly TGFβ could regulate fibroblast differentiation and proliferation through paracrine and autocrine regulation to promote wound healing.…”

Section: Discussionmentioning

confidence: 99%

Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

Zhu

Dong

2022

J of Cosmetic Dermatology

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Objective: Poly-L-Lactic Acid (PLLA) is a synthetic polymer which possesses biocompatible and biodegradable properties, and is widely used in the clinical filler material.This study focuses on the potential role of PLLA on the collagen production of dermal fibroblasts and its mechanism. Methods:The dermal fibroblast Hs60 was treated with different concentration of PLLA. RT-qPCR was conducted for the determination of mRNA levels of collagen type I (COL1) alpha 1 (COL1A1), COL1 alpha 2 (COL1A2), elastin, matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2. Procollagen Type I C-peptide (PIP) enzyme immunoassay (EIA) Kit assay was carried out to analyze procollagen production. Western Blot was employed to examine the effect of PLLA and transforming frown factor (TGFβ) receptor-specific inhibitor (SB431542) on protein levels of COL1A1 and TGFβ/Smad signaling pathway related proteins.Results: With the increase of PLLA concentration, the production of procollagen gradually increased, and both protein and mRNA levels of COL1A1 and COL1A2 gradually increased (p < 0.001). Elevated PLLA concentrations increased elastin, TIMP-1, and TIMP-2 levels and attenuated MMP-1 expression. PLLA increased TGFβ levels in a dose-dependently manner. p-Smad2 and p-Smad3 protein levels were also increased by PLLA, but the influences were reversed by SB431542 (p < 0.001). Similarly, increased levels of COL1A1, COL1A2, TIMP-1, and TIMP-2 caused by PLLA were significantly inhibited by SB431542, whereas MMP-1 was typically elevated (p < 0.001). Conclusion:Poly-L-Lactic Acid promotes the collagen production of dermal fibroblasts by activating the TGFβ/Smad signaling pathway. The findings may lay a foundation for clinical material applications of PLLA.

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IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

Chang

Lee

Yang

et al. 2023

Biochemical Pharmacology

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IOX1 protects from TGF‑β induced fibrosis in LX‑2 cells via the regulation of extracellular matrix protein expression

Cited by 4 publications

References 31 publications

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

IOX-1 suppresses metastasis of osteosarcoma by upregulating histone H3 lysine trimethylation

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