Gene expression analysis of zebrafish heart regeneration.
Mammalian hearts cannot regenerate. In contrast, zebrafish hearts regenerate even when up to 20% of the ventricle is amputated. The mechanism of zebrafish heart regeneration is not understood. To systematically characterize this process at the molecular level, we generated transcriptional profiles of zebrafish cardiac regeneration by microarray analyses. Distinct gene clusters were identified based on temporal expression patterns. Genes coding for wound response/inflammatory factors, secreted molecules, and matrix metalloproteinases are expressed in regenerating heart in sequential patterns. Comparisons of gene expression profiles between heart and fin regeneration revealed a set of regeneration core molecules as well as tissue-specific factors. The expression patterns of several secreted molecules around the wound suggest that they play important roles in heart regeneration. We found that both platelet-derived growth factor-a and -b (pdgf-a and pdgf-b) are upregulated in regenerating zebrafish hearts. PDGF-B homodimers induce DNA synthesis in adult zebrafish cardiomyocytes. In addition, we demonstrate that a chemical inhibitor of PDGF receptor decreases DNA synthesis of cardiomyocytes both in vitro and in vivo during regeneration. Our data indicate that zebrafish heart regeneration is associated with sequentially upregulated wound healing genes and growth factors and suggest that PDGF signaling is required.
Lien
Ching-Ling
CL
Department of Cardiology, Children's Hospital, Boston, Massachusetts, USA. lien@enders.tch.harvard.edu
Schebesta
Michael
M
Makino
Shinji
S
Weber
Gerhard J
GJ
Keating
Mark T
MT
D000818:Animals; D000077214:Becaplermin; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D020571:Genes, sis; D006321:Heart / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012038:Regeneration / Q000235:genetics*; D015398:Signal Transduction; D015854:Up-Regulation; D015027:Zebrafish / Q000235:genetics* / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D029961:Zebrafish Proteins; C075278:platelet-derived growth factor A; D000077214:Becaplermin; D020782:Matrix Metalloproteinases