Receptors, Volume 4, Issue 4 (December 2025) – 3 articles

Background: PIEZO channels are mechanoreceptors expressed in various cells. Their contributions to animal development are not entirely clear. According to the physical distortion hypothesis, developmental organizers for butterfly wing eyespots receive and release mechanical signals in pupal wing tissues during development, initiating a calcium signaling cascade and gene expression changes. Objectives: We tested the possible involvement of PIEZO1 in butterfly wing color pattern formation, according to the physical distortion hypothesis. Methods: We performed a pharmacological intervention of PIEZO1, focusing on the eyespots of Junonia orithya. Chemical modulators of PIEZO1 and the actin cytoskeleton were injected into pupae immediately after pupation during the critical period of color pattern determination, and the eyespot color patterns of the emerging adult wings were analyzed. We also tested dimethyl sulfoxide (DMSO) because it was used as a solvent. Results: DMSO significantly enlarged most eyespots examined. In contrast, the specific PIEZO1 activator Jedi2 induced significant reduction in the dorsal hindwing eyespots. Another specific PIEZO1 activator, Yoda1, also induced similar changes, although less clearly. The mechanosensitive channel blocker GsMTx4 produced compromised eyespots in an individual, although statistical support for modification was weak. The actin polymerization activator phalloidin induced blue foci in the ventral forewing eyespots. PIEZO expression in the pupal wings was demonstrated by RT-PCR. Conclusions: These results suggest that eyespot organizers in butterfly wings may employ a PIEZO-mediated mechanotransduction pathway to regulate eyespot color patterns, supporting the physical distortion hypothesis. These results highlight the importance of PIEZO in developmental organizers in animals. Full article

Adipocyte cell models are essential for investigating adipogenesis, yet methodological inconsistencies pose challenges to obtaining reproducible and physiologically relevant results. Murine cell lines, such as 3T3-L1 and OP9, are commonly utilized due to their established adipogenic capabilities. However, differences in its metabolic, genetic regulation, and receptor signaling raise concerns about their applicability to human adipose biology. Human-derived models, including mesenchymal stem cells (hMSCs) and preadipocyte cell lines, offer a closer approximation to in vivo adipogenesis but display significant variability in differentiation efficiency. This variability is often compounded by heterogeneous differentiation protocols, variations in cell confluence, and unstandardized pharmacological induction strategies. A pivotal factor influencing adipogenic potential is the receptor toolkit, which dictates cellular responses to differentiation stimuli. This study systematically evaluates key receptors—PPARγ, glucocorticoid receptors (GR), insulin receptor (IR), thyroid hormone receptors (TR), estrogen receptors (ER), and adenosine receptors (AR)—across commonly used adipocyte models to assess their roles in adipogenic regulation. Additionally, we examine the impact of pharmacological agents capable of inducing adipogenesis (adipogens) and the methodological inconsistencies that contribute to variations in adipocyte differentiation. By addressing these factors, we aim to elucidate the extent to which receptor variability influences experimental outcomes and propose a more structured approach to interpreting adipogenesis research. This critical assessment underscores the need for greater methodological transparency and receptor profiling to enhance the reliability of adipocyte models in metabolic research. Standardizing differentiation methodologies while accounting for receptor diversity will be essential for refining in vitro models and improving their translational potential in the study of obesity, diabetes, and other metabolic disorders. Full article

Background: HER1 and HER2 are critical receptors involved in tumorigenesis and the development of targeted therapies for various carcinomas. However, most antibodies and drugs currently in development do not recognize murine orthologs, which restricts their evaluation in immunocompetent models. Methods: We generated nine tumor models through the lentiviral transduction of murine prostate (RM1), lung (3LL-D122), and breast (4T1) carcinoma cell lines, subsequently validating them in immunocompetent BALB/c and C57BL/6 hosts. Receptor expression and functionality were characterized using flow cytometry, immunoblotting, proliferation assays, and therapeutic sensitivity testing. Results: Transduced cells exhibited stable membrane expression of HER1/HER2 and ligand-induced phosphorylation, confirming receptor functionality. In all three tumor models generated, the expression of HER1 and/or HER2 significantly enhanced cell proliferation compared to parental lines. Furthermore, treatment with specific monoclonal antibodies and the tyrosine kinase inhibitor markedly reduced the viability of cells expressing HER1 and/or HER2, without affecting negative controls. Conclusions: These models provide a robust and reproducible platform for the preclinical evaluation of HER1/HER2-targeted therapies in immunocompetent hosts. Although the current model relies on subcutaneous implantation and does not fully replicate the native tumor microenvironment, it represents a crucial first step toward the development of orthotopic and immunologically relevant models for translational cancer research. Full article