microRNA Expression Profile of Purified Alveolar Epithelial Type II Cells.

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways.

Intrauterine smoke exposure deregulates lung function, pulmonary transcriptomes, and in particular insulin-like growth factor (IGF)-1 in a sex-specific manner.

Prenatal exposure to tobacco smoke is a significant risk-factor for airway disease development. Furthermore, the high prevalence of pregnant smoking women requires the establishment of strategies for offspring lung protection. Therefore, we here aimed to understand the molecular mechanism of how prenatal smoke exposure affects fetal lung development.

Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition.

Introduction: Placental fatty acid (FA) uptake and metabolism depend on maternal supply which may be altered when women have a high pre-pregnancy body mass index (BMI) or develop gestational diabetes (GDM). Consequently, an impaired FA transport to the fetus may negatively affect fetal development. While placental adaptation of maternal-fetal glucose transfer in mild GDM has been described, knowledge on placental FA acid metabolism and possible adaptations in response to maternal obesity or GDM is lacking.

D-tryptophan from probiotic bacteria influences the gut microbiome and allergic airway disease.

Background: Chronic immune diseases, such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals, such as probiotics, for the prevention of allergic disease.

Validated prediction of pro-invasive growth factors using a transcriptome-wide invasion signature derived from a complex 3D invasion assay.

The invasion of activated fibroblasts represents a key pathomechanism in fibrotic diseases, carcinogenesis and metastasis. Invading fibroblasts contribute to fibrotic extracellular matrix (ECM) formation and the initiation, progression, or resistance of cancer. To construct transcriptome-wide signatures of fibroblast invasion, we used a multiplex phenotypic 3D invasion assay using lung fibroblasts.

Inter- and transgenerational epigenetic inheritance: evidence in asthma and COPD?

Evidence is now emerging that early life environment can have lifelong effects on metabolic, cardiovascular, and pulmonary function in offspring, a concept also known as fetal or developmental programming. In mammals, developmental programming is thought to occur mainly via epigenetic mechanisms, which include DNA methylation, histone modifications, and expression of non-coding RNAs. The effects of developmental programming can be induced by the intrauterine environment, leading to intergenerational epigenetic effects from one generation to the next.

MicroRNA methodology: advances in miRNA technologies.

There is an emerging trend in microRNA research and thus substantial progress in microRNA technologies. In this chapter we provide insights into the main microRNA specific methodologies and critical steps of microRNA expression profiling, target gene identification, and functional confirmation of microRNA effects up to in vivo application of antagomirs.

Of flies, mice and men: a systematic approach to understanding the early life origins of chronic lung disease.

Despite intensive research efforts, the aetiology of the majority of chronic lung diseases (CLD) in both, children and adults, remains elusive. Current therapeutic options are limited, providing only symptomatic relief, rather than treating the underlying condition, or preventing its development in the first place. Thus, there is a strong and unmet clinical need for the development of both, novel effective therapies and preventative strategies for CLD.

Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection.

Rhoh is a hematopoietic system-specific GTPase. Rhoh-deficient T cells have been shown to have a defect in TCR signaling manifested during their thymic development. Our aims were to investigate the phenotype of peripheral Rhoh-deficient T cells and to explore in vivo the potential benefit of Rhoh deficiency in a clinically relevant situation, in which T-cell inhibition is desirable.

Chemokine receptor Ccr5 deficiency induces alternative macrophage activation and improves long-term renal allograft outcome.

The chemokine (C-C motif) receptor 5 (CCR5) has been implicated in experimental and clinical allograft rejection. To dissect the function of CCR5 in acute and chronic renal allograft rejection, bilaterally nephrectomized WT and Ccr5-/- C57BL/6 mice were used as recipients of WT BALB/c renal allografts and analyzed 7 and 42 days after transplantation. Lesion scores (glomerular damage, vascular rejection, tubulointerstitial inflammation) and numbers of CD4+, CD8+, CD11c+ and alpha smooth muscle actin (alphaSMA)+ cells were reduced in allografts from Ccr5-/- recipients during the chronic phase.

Microinjection of Cre recombinase protein into zygotes enables specific deletion of two eukaryotic selection cassettes and enhances the expression of a DsRed2 reporter gene in Ccr2/Ccr5 double-deficient mice.

The chemokine receptors CCR2 and CCR5 represent potential novel therapeutic targets to treat important inflammatory and infectious diseases, including atherosclerosis and HIV infection. To study the functions of both receptors in vivo, we aimed to generate Ccr2/Ccr5 double-deficient mice. As these genes are separated by <20 kb, they were inactivated consecutively by two rounds of gene targeting in embryonic stem (ES) cells.