Drosophila suzukii is threatening soft fruit production worldwide due to the females’ ability to pierce through the intact skin of ripe fruits and lay eggs inside. Larval consumption and the associated microbial infection cause rapid fruit degradation, thus drastic yield and economic loss. Cultivars that limit the proliferation of flies may be ideal to counter this pest; however, they have not yet been developed or identified. To search for potential breeding material, we investigated the rate of adult D. suzukii emergence from individual fruits (fly emergence) of 107 accessions of Fragaria species that had been exposed to egg-laying D. suzukii females. We found significant variation in fly emergence across strawberries, which correlated with accession and fruit diameter, and to a lesser extent with the strawberry species background. We identified accessions with significantly reduced fly emergence, not explained by their fruit diameter. These accessions constitute valuable breeding material for strawberry cultivars that limit D. suzukii spread.

Sustained exposure of the lung to various environmental or occupational toxins may eventually lead to pulmonary fibrosis, a devastating disease with no cure. Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix (ECM) proteins such as fibronectin and collagens. The peptidase plasmin degrades the ECM, but protein levels of the plasmin activator inhibitor-1 (PAI-1) are increased in fibrotic lung tissue, thereby dampening plasmin activity. Transforming growth factor-β1 (TGF-β1)-induced activation of SMAD transcription factors promotes ECM deposition by enhancing collagen, fibronectin and PAI-1 levels in pulmonary fibroblasts. Hence, counteracting TGF-β1-induced signaling is a promising approach for the therapy of pulmonary fibrosis. Transient receptor potential cation channel subfamily M Member 7 (TRPM7) supports TGF-β1-promoted SMAD signaling in T-lymphocytes and the progression of fibrosis in kidney and heart. Thus, we investigated possible effects of TRPM7 on plasmin activity, ECM levels and TGF-β1 signaling in primary human pulmonary fibroblasts (pHPF). We found that two structurally unrelated TRPM7 blockers enhanced plasmin activity and reduced fibronectin or PAI-1 protein levels in pHPF under basal conditions. Further, TRPM7 blockade strongly inhibited fibronectin and collagen deposition induced by sustained TGF-β1 stimulation. In line with these data, inhibition of TRPM7 activity diminished TGF-β1-triggered phosphorylation of SMAD-2, SMAD-3/4-dependent reporter activation and PAI-1 mRNA levels. Overall, we uncover TRPM7 as a novel supporter of TGF-β1 signaling in pHPF and propose TRPM7 blockers as new candidates to control excessive ECM levels under pathophysiological conditions conducive to pulmonary fibrosis.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca 2+ permeable cation channel, which was originally cloned from human lung fibroblasts (HLFs). TRPA1-mediated Ca2+ entry is evoked by exposure to several chemicals, including allyl isothiocyanate (AITC), and a protective effect of TRPA1 activation in the development of cardiac fibrosis has been proposed. Yet, the function of TRPA1 in transforming growth factor β1 (TGF-β1)-driven fibroblast to myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function was analyzed in cultured primary HLFs, and mRNA levels were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers, e.g. alpha smooth muscle actin (ACTA2), plasminogen activator inhibitor 1 (SERPINE1), fibronectin (FN1) and type I collagen (COL1A1) was increased after siRNA-mediated down-regulation of TRPA1-mRNA in HLFs. Moreover, AITC-induced Ca 2+ entry in HLFs was decreased after TGF-β1 treatment and by application of TRPA1 siRNAs, while AITC treatment alone did not reduce cell viability or enhanced apoptosis. Cell barrier function increased after addition of TRPA1 siRNAs or TGF-β1 treatment. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 phosphorylation, which might inhibit TGF-β-receptor signaling. Our results suggest an inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation. Therefore, activation of TRPA1 channels might be protective during the development of pulmonary fibrosis in patients.

Glucose provides vital energy for cells and contributes to gene expression. The hypothalamus is key for metabolic homeostasis, but effects of glucose on hypothalamic gene expression have not yet been investigated in detail. Thus, herein, we monitored the glucose-dependent transcriptome in murine hypothalamic mHypoA-2/10 cells by total RNA-seq analysis. A total of 831 genes were up- and 1390 genes were downregulated by at least 50%. Key genes involved in the cholesterol biosynthesis pathway were upregulated, and total cellular cholesterol levels were significantly increased by glucose. Analysis of single genes involved in fundamental cellular signaling processes also suggested a significant impact of glucose. Thus, we chose ≈100 genes involved in signaling and validated the effects of glucose on mRNA levels by qRT-PCR. We identified Gnai1–3, Adyc6, Irs1, Igfr1, Hras, and Elk3 as new glucose-dependent genes. In line with this, cAMP measurements revealed enhanced noradrenalin-induced cAMP levels, and reporter gene assays elevated activity of the insulin-like growth factor at higher glucose levels. Key data of our studies were confirmed in a second hypothalamic cell line. Thus, our findings link extra cellular glucose levels with hypothalamic lipid synthesis and pivotal intracellular signaling processes, which might be of particular interest in situations of continuously increased glucose levels.

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca2+ permeable cation channel, which was originally cloned from human lung fibroblasts (HLFs). TRPA1-mediated Ca2+ entry is evoked by exposure to several chemicals, including allyl isothiocyanate (AITC), and a protective effect of TRPA1 activation in the development of cardiac fibrosis has been proposed. Yet, the function of TRPA1 in transforming growth factor β1 (TGF-β1)-driven fibroblast to myofibroblast differentiation and the development of pulmonary fibrosis remains elusive. TRPA1 expression and function was analyzed in cultured primary HLFs, and mRNA levels were significantly reduced after adding TGF-β1. Expression of genes encoding fibrosis markers, e.g. alpha smooth muscle actin (ACTA2), plasminogen activator inhibitor 1 (SERPINE1), fibronectin (FN1) and type I collagen (COL1A1) was increased after siRNA-mediated down-regulation of TRPA1-mRNA in HLFs. Moreover, AITC-induced Ca2+ entry in HLFs was decreased after TGF-β1 treatment and by application of TRPA1 siRNAs, while AITC treatment alone did not reduce cell viability or enhanced apoptosis. Cell barrier function increased after addition of TRPA1 siRNAs or TGF-β1 treatment. Most interestingly, AITC-induced TRPA1 activation augmented ERK1/2 phosphorylation, which might inhibit TGF-β-receptor signaling. Our results suggest an inhibitory function of TRPA1 channels in TGF-β1-driven fibroblast to myofibroblast differentiation. Therefore, activation of TRPA1 channels might be protective during the development of pulmonary fibrosis in patients.