Growth hormone modulates epithelial intercellular junctions structure and intestinal permeability in zebrafish

Author(s)

Meirelles, Marcela G. ; Fenero, Camila I. M. ; Nornberg, Bruna F. ; da Silveira, Tony L. R. ; Kutter, Mateus T. ; Camara, Niels Olsen S. ; Marins, Luis Fernando

• Document type: Journal article
• Source: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY; v. 310, p. 9-pg., 2025-12-01.

Abstract

Intestinal permeability refers to the regulated passage of luminal contents into the internal milieu via transcellular or paracellular routes. Tight junctions (TJs), components of the apical junctional complex (AJC), are critical determinants of paracellular permeability and intestinal barrier integrity. Disruptions in growth hormone (GH) signaling have been implicated in gastrointestinal dysfunction; however, the effects of chronically elevated GH levels on intestinal barrier function remain poorly understood. In this study, we investigated whether GH overexpression affects intestinal permeability and epithelial structure using a transgenic zebrafish model. ghtransgenic zebrafish and their non-transgenic full siblings were evaluated for intestinal architecture and barrier function. Images of transmission electron microscopy revealed a greater frequency of AJC disruption in ghtransgenic fish. These ultrastructural changes were associated with increased transcription of TJ-related genes, including cldn15a, oclna, and zo1a, as assessed by qRT-PCR, and a higher intestinal permeability to macromolecule (RITC-dextran 10,000 MW). These findings demonstrate that chronic gh overexpression alters intercellular epithelial architecture and enhances intestinal paracellular permeability. This may reflect an adaptive mechanism to meet increased energy demands under anabolic conditions. Moreover, these results suggest a mechanistic link between GH signaling pathways and modulation of the intestinal barrier, with potential implications for biomedical science. (AU)

• FAPESP's process: 15/21644-9 - Obesity-induced inflammation, alterations in the microbiota and their effects on the enteric nervous system: study in an experimental model of zebrafish.
• Grantee: Camila Idelí Morales Fénero
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants