Background: Relaxin/relaxin family peptide receptor 1 (RXFP1) signaling is important for both normal physiology and disease. Strong preclinical evidence supports relaxin as a potent antifibrotic molecule. However, relaxin-based therapy failed in clinical trial in patients with systemic sclerosis. We and others have discovered that aberrant expression of RXFP1 may contribute to the abnormal relaxin/RXFP1 signaling in different diseases. Reduced RXFP1 expression and alternative splicing transcripts with potential functional consequences have been observed in fibrotic tissues.A relative decrease in RXFP1 expression in fibrotic tissues-specifically lung and skin-may explain a potential insensitivity to relaxin. In addition, receptor dimerization also plays important roles in relaxin/RXFP1 signaling. Methods: This review describes the tissue specific expression, characteristics of the splicing variants, and homo/heterodimerization of RXFP1 in both normal physiological function and human diseases. We discuss the potential implications of these molecular features for developing therapeutics to restore relaxin/RXFP1 signaling and to harness relaxin's potential antifibrotic effects. Results: Relaxin/RXFP1 signaling is important in both normal physiology and in human diseases. Reduced expression of RXFP1 in fibrotic lung and skin tissues surrenders both relaxin/RXFP1 signaling and their responsiveness to exogenous relaxin treatments. Alternative splicing and receptor dimerization are also important in regulating relaxin/RXFP1 signaling. Conclusions: Understanding the molecular mechanisms that drive aberrant expression of RXFP1 in disease and the functional roles of alternative splicing and receptor dimerization will provide insight into therapeutic targets that may restore the relaxin responsiveness of fibrotic tissues. K E Y W O R D S alternative splicing, fibrosis, relaxin, RXFP1While much is known about the cell signaling pathways activated by relaxin, it is clear that ligand-receptor interactions are multidimensional and represent a potential site for cell signaling regulation. In experimental binding assays, relaxin dose, treatment length, and assay temperature contributed to the efficiency of relaxin binding to its receptor (Svendsen

Idiopathic pulmonary fibrosis (IPF) is characterized by altered epithelial cell phenotypes, which are associated with myofibroblast accumulation in the lung. Atypical alveolar epithelial cells in IPF express molecular markers of airway epithelium. Polymorphisms within and around Toll interacting protein (TOLLIP) are associated with the susceptibility to IPF and mortality. However, the functional role of TOLLIP in IPF is unknown. Using lung tissues from IPF and control subjects, we showed that expression of TOLLIP gene in the lung parenchyma is globally lower in IPF compared to controls. Lung cells expressing significant levels of TOLLIP include macrophages, alveolar type II, and basal cells. TOLLIP protein expression is lower in the parenchyma of IPF lungs but is expressed in the atypical epithelial cells of the distal fibrotic regions. Using overexpression and silencing approaches, we demonstrate that TOLLIP protects cells from bleomycin-induced apoptosis using primary | 9885 LI et aL.

We demonstrate a flexible transmissive color filter based on a hybrid metallic–optical Tamm state device composed of a thin metallic film on top of dual dielectric distributed Bragg reflectors (DBRs) to simultaneously excite the Tamm plasmon (TP), the optical Tamm state (OTS), and the Fabry–Pérot (FP) resonant eigenmodes for spectrally achieving triple transmittance peaks in the visible light range. We show that the resonant eigenmodes confined inside the device can be tuned at will by simply adjusting the designed Bragg wavelengths of the dual DBRs and retain an ultranarrow bandwidth regardless of resonant wavelength, creating the desired chromaticity points and constructing a large color gamut space in the CIE coordinate. We further show that, due to the fabrication simplicity of our color filter involving only thin-film deposition, the proposed structure can be easily integrated onto flexible substrates, leading to tunable transmittance spectrum as well as the color appearance by simply changing its bending curvature. The tunable color filter reported herein can be employed for various applications such as aesthetical color decorations in architectures, low-cost and portable spectral analyzers, and optical strain/deformation sensors.