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Lysyl Hydroxylase 3 Increases Collagen Deposition and Promotes Pulmonary Fibrosis by Activating TGFβ1/Smad3 and Wnt/β-catenin Pathways

Lysyl Hydroxylase 3 Increases Collagen Deposition and Promotes Pulmonary Fibrosis by Activating TGFβ1/Smad3 and Wnt/β-catenin Pathways

Songjun Shao, Haiyan Fang, Lindi Duan, Xianwei Ye, Shanshan Rao, Jin Han, Yumei Li, Guohang Yuan, Weijia Liu, Xiangyan Zhang

Arch Med Sci. 2019 Jan 16;16(2):436-445.

PMID: 32190155

Abstract:

Introduction:
Lysyl hydroxylase 3 (LH3) is a collagen post-translational modifying enzyme; it is abnormally activated during the formation of collagen cross-links. iCRT3 is an inhibitor of both Wnt and β-catenin responsive transcription. We hypothesized that LH3 is regulated by TGFβ1/Smad3 signaling and Wnt/β-catenin signaling pathways. Some evidence suggested that there is complicated cross-talk between the two signal pathways in the genesis of pulmonary fibrosis.
Material and methods:
The normal culturing human lung cancer cell line A549 was derived from pulmonary epithelial cells. Transforming growth factor-β1 (TGF-β1) was induced A549 cells of pulmonary fibrosis. MTT assays detected cell growth stimulation by TGF-β1; collagen pyridine-crosslinking contents were detected by ELISA kits. Immunofluorescence were used to evaluate expression of key molecules in PLOD3 (LH3), Wnt/β-catenin and TGFβ1/Smad3 pathways.
Results:
Our findings suggested that iCRT3 could decrease LH3 protein expression (p < 0.01), Wnt1, β-catenin and p-Smad3 protein expression (p < 0.05). Knock-down PLOD3 could decrease LH3, collagen I gene and protein expression (p < 0.05). These effects were associated with decreasing collagen pyridine-crosslinking production (p < 0.05). However, ovexpression PLOD3 could increase LH3, collagen I gene and protein expression (p < 0.05). The result showed that LH3 plays an important role in collagen post-translational modifications, and it is regulated by Wnt/β-catenin and TGFβ1/Smad3 pathways.
Conclusions:
This study suggests that PLOD3 (LH3) represents a target to prevent pulmonary fibrosis.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP901751471	iCRT3		901751-47-1	Price

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