A novel zebrafish model to emulate lung injury by folate deficiency-induced swim bladder defectiveness and protease/antiprotease expression imbalance

Gang-Hui Lee, Nai Wei Cheng, Hsin Hsuan Yu, Jen Ning Tsai, Tsunglin Liu, Zhi Hong Wen, Bing Hung Chen, Tzu-Fun Fu

Research output: Contribution to journalArticle

Abstract

Lung injury is one of the pathological hallmarks of most respiratory tract diseases including asthma, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). It involves progressive pulmonary tissue damages which are usually irreversible and incurable. Therefore, strategies to facilitate drug development against lung injury are needed. Here, we characterized the zebrafish folate-deficiency (FD) transgenic line that lacks a fully-developed swim bladder. Whole-mount in-situ hybridization revealed comparable distribution patterns of swim bladder tissue markers between wild-type and FD larvae, suggesting a proper development of swim bladder in early embryonic stages. Unexpectedly, neutrophils infiltration was not observed in the defective swim bladder. Microarray analysis revealed a significant increase and decrease of the transcripts for cathepsin L and a cystatin B (CSTB)-like (zCSTB-like) proteins, respectively, in FD larvae. The distribution of cathepsin L and the zCSTB-like transcripts was spatio-temporally specific in developing wild-type embryos and, in appropriate measure, correlated with their potential roles in maintaining swim bladder integrity. Supplementing with 5-formyltetrahydrofolate successfully prevented the swim bladder anomaly and the imbalanced expression of cathepsin L and the zCSTB-like protein induced by folate deficiency. Injecting the purified recombinant zebrafish zCSTB-like protein alleviated FD-induced swim bladder anomaly. We concluded that the imbalanced expression of cathepsin L and the zCSTB-like protein contributed to the swim bladder malformation induced by FD and suggested the potential application of this transgenic line to model the lung injury and ECM remodeling associated with protease/protease inhibitor imbalance.

Original languageEnglish
Article number12633
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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Lung Injury
Zebrafish
Protease Inhibitors
Folic Acid
Urinary Bladder
Peptide Hydrolases
Cathepsin L
Larva
Cystatin B
Proteins
Respiratory Tract Diseases
Leucovorin
Neutrophil Infiltration
Adult Respiratory Distress Syndrome
Microarray Analysis
Chronic Obstructive Pulmonary Disease
In Situ Hybridization
Asthma
Embryonic Structures
Lung

All Science Journal Classification (ASJC) codes

  • General

Cite this

Lee, Gang-Hui ; Cheng, Nai Wei ; Yu, Hsin Hsuan ; Tsai, Jen Ning ; Liu, Tsunglin ; Wen, Zhi Hong ; Chen, Bing Hung ; Fu, Tzu-Fun. / A novel zebrafish model to emulate lung injury by folate deficiency-induced swim bladder defectiveness and protease/antiprotease expression imbalance. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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A novel zebrafish model to emulate lung injury by folate deficiency-induced swim bladder defectiveness and protease/antiprotease expression imbalance. / Lee, Gang-Hui; Cheng, Nai Wei; Yu, Hsin Hsuan; Tsai, Jen Ning; Liu, Tsunglin; Wen, Zhi Hong; Chen, Bing Hung; Fu, Tzu-Fun.

In: Scientific reports, Vol. 9, No. 1, 12633, 01.12.2019.

Research output: Contribution to journalArticle

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AU - Cheng, Nai Wei

AU - Yu, Hsin Hsuan

AU - Tsai, Jen Ning

AU - Liu, Tsunglin

AU - Wen, Zhi Hong

AU - Chen, Bing Hung

AU - Fu, Tzu-Fun

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