Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration

• Published in: Molecular biology reports Vol. 51; no. 1; p. 604
• Main Authors: Lai, Zih-Yin, Yang, Chung-Chi, Chen, Po-Hsun, Chen, Wei-Chen, Lai, Ting-Yu, Lu, Guan-Yun, Yang, Chiao-Yu, Wang, Ko-Ying, Liu, Wei-Cen, Chen, Yu-Chieh, Liu, Lawrence Yu-Min, Chuang, Yung-Jen
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2024; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Animals; Biomedical and Life Sciences; Cell proliferation; Cell Proliferation - genetics; Cryoinjury; Danio rerio; EKG; Extracellular matrix; Fibronectin; Gene Knockdown Techniques; Heart; Heart - physiology; Heart - physiopathology; Histology; Inflammation; Life Sciences; Matrix protein; Morphology; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardium - metabolism; Myocardium - pathology; Original; Original Article; Regeneration - genetics; Syndecan; Syndecan-4 - genetics; Syndecan-4 - metabolism; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Heart regeneration; Zebrafish; Syndecan-4; Repair response
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-024-09531-4

Background
The healing process after a myocardial infarction (MI) in humans involves complex events that replace damaged tissue with a fibrotic scar. The affected cardiac tissue may lose its function permanently. In contrast, zebrafish display a remarkable capacity for scar-free heart regeneration. Previous studies have revealed that syndecan-4 (SDC4) regulates inflammatory response and fibroblast activity following cardiac injury in higher vertebrates. However, whether and how Sdc4 regulates heart regeneration in highly regenerative zebrafish remains unknown.
Methods and Results
This study showed that
sdc4
expression was differentially regulated during zebrafish heart regeneration by transcriptional analysis. Specifically,
sdc4
expression increased rapidly and transiently in the early regeneration phase upon ventricular cryoinjury. Moreover, the knockdown of
sdc4
led to a significant reduction in extracellular matrix protein deposition, immune cell accumulation, and cell proliferation at the lesion site. The expression of
tgfb1a
and
col1a1a
, as well as the protein expression of Fibronectin, were all down-regulated under
sdc4
knockdown. In addition, we verified that
sdc4
expression was required for cardiac repair in zebrafish via in vivo electrocardiogram analysis. Loss of
sdc4
expression caused an apparent pathological Q wave and ST elevation, which are signs of human MI patients.
Conclusions
Our findings support that Sdc4 is required to mediate pleiotropic repair responses in the early stage of zebrafish heart regeneration.