The Relaxin Gene Knockout Mouse: A Model of Progressive Scleroderma

Relaxin is a peptide hormone with anti-fibrotic properties. To investigate the long-term effects of relaxin deficiency on the ageing skin, we compared structural changes in the skin of ageing relaxin-deficient (RLX-/-) and normal (RLX+/+) mice, by biochemical, histological, and magnetic resonance imaging analyses. Skin biopsies from RLX+/+ and RLX-/- mice were obtained at different ages and analyzed for changes in collagen expression and distribution. We demonstrated an age-related progression of dermal fibrosis and thickening in male and female RLX-/- mice, associated with marked increases in types I and III collagen. The increased collagen was observed primarily in the dermis of RLX-/- mice by 1 mo of age, and eventually superseded the hypodermal layer. Additionally, fibroblasts from the dermis of RLX-/- mice were shown to produce increased collagen in vitro. Recombinant human gene-2 (H2) relaxin treatment of RLX-/- mice resulted in the complete reversal of dermal fibrosis, when applied to the early onset of disease, but was ineffective when applied to more established stages of dermal scarring. These combined findings demonstrate that relaxin provides a means to regulate excessive collagen deposition in disease states characterized by dermal fibrosis and with our previously published work demonstrate the relaxin-null mouse as a model of progressive scleroderma

Relaxin-1–deficient mice develop an age-related progression of renal fibrosis

Relaxin-1–deficient mice develop an age-related progression of renal fibrosis.BackgroundRelaxin (RLX) is a peptide hormone that stimulates the breakdown of collagen in preparation for parturition and when administered to various models of induced fibrosis. However, its significance in the aging kidney is yet to be established. In this study, we compared structural and functional changes in the kidney of aging relaxin-1 (RLX-/-) deficient mice and normal (RLX+/+) mice.MethodsThe kidney cortex and medulla of male and female RLX+/+ and RLX-/- mice at various ages were analyzed for collagen content, concentration, and types. Histologic analysis, reverse transcription-polymerase chain reaction (RT-PCR) of relaxin and relaxin receptor mRNA expression, receptor autoradiography, glomerular isolation/analysis, and serum/urine analysis were also employed. Relaxin treatment of RLX-/- mice was used to confirm the antifibrotic effects of the peptide.ResultsWe demonstrate an age-related progression of renal fibrosis in male, but not female, RLX-/- mice with significantly (P < 0.05) increased tissue dry weight, collagen (type I) content and concentration. The increased collagen expression in the kidney was associated with increased glomerular matrix and to a lesser extent, interstitial fibrosis in RLX-/- mice, which also had significantly increased serum creatinine (P < 0.05) and urinary protein (P < 0.05). Treatment of RLX-/- mice with relaxin in established stages of renal fibrosis resulted in the reversal of collagen deposition.ConclusionThis study supports the concept that relaxin may provide a means to regulate excessive collagen deposition during kidney development and in diseased states characterized by renal fibrosis

Relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to up-regulate matrix metalloproteinases: the additional involvement of iNOS

The hormone, relaxin, inhibits aberrant myofibroblast differentiation and collagen deposition by disrupting the TGF-β1/Smad2 axis, via its cognate receptor, Relaxin Family Peptide Receptor 1 (RXFP1), extracellular signal-regulated kinase (ERK)1/2 phosphorylation (pERK) and a neuronal nitric oxide (NO) synthase (nNOS)-NO-cyclic guanosine monophosphate (cGMP)-dependent pathway. However, the signalling pathways involved in its additional ability to increase matrix metalloproteinase (MMP) expression and activity remain unknown. This study investigated the extent to which the NO pathway was involved in human gene-2 (H2) relaxin's ability to positively regulate MMP-1 and its rodent orthologue, MMP-13, MMP-2 and MMP-9 (the main collagen-degrading MMPs) in TGF-β1-stimulated human dermal fibroblasts and primary renal myofibroblasts isolated from injured rats; by gelatin zymography (media) and Western blotting (cell layer). H2 relaxin (10-100 ng/ml) significantly increased MMP-1 (by ~50%), MMP-2 (by ~80%) and MMP-9 (by ~80%) in TGF-β1-stimulated human dermal fibroblasts; and MMP-13 (by ~90%), MMP-2 (by ~130%) and MMP-9 (by ~115%) in rat renal myofibroblasts (all p<0.01 vs untreated cells) over 72 hours. The relaxin-induced up-regulation of these MMPs, however, was significantly blocked by a non-selective NOS inhibitor (L-nitroarginine methyl ester (hydrochloride); L-NAME; 75-100 µM), and specific inhibitors to nNOS (N-propyl-L-arginine; NPLA; 0.2-2 µM), iNOS (1400W; 0.5-1 µM) and guanylyl cyclase (ODQ; 5 µM) (all p<0.05 vs H2 relaxin alone), but not eNOS (L-N-(1-iminoethyl)ornithine dihydrochloride; L-NIO; 0.5-5 µM). However, neither of these inhibitors affected basal MMP expression at the concentrations used. Furthermore, of the NOS isoforms expressed in renal myofibroblasts (nNOS and iNOS), H2 relaxin only stimulated nNOS expression, which in turn, was blocked by the ERK1/2 inhibitor (PD98059; 1 µM). These findings demonstrated that H2 relaxin signals through a RXFP1-pERK-nNOS-NO-cGMP-dependent pathway to mediate its anti-fibrotic actions, and additionally signals through iNOS to up-regulate MMPs; the latter being suppressed by TGF-β1 in myofibroblasts, but released upon H2 relaxin-induced inhibition of the TGF-β1/Smad2 axis

Controllable Growth of Lead-Free All-Inorganic Perovskite Nanowire Array with Fast and Stable Near-Infrared Photodetection

Low-dimensional all-inorganic metal halide perovskites have been demonstrated as excellent building blocks for high-performance optoelectronic devices. Although many progresses have been achieved in low-dimensional all-inorganic perovskites, the substitution of toxic Pb is urgent for further optoelectronic applications. Here, we present the growth of lead-free all-inorganic CsSnX3 (X = Cl, Br, and I) perovskite nanowire (NW) arrays on a mica substrate by a solid-source chemical vapor deposition method. All of the lead-free all-inorganic CsSnX3 perovskite NW arrays epitaxially grow on the mica substrate to form equilateral triangles. The band gaps of the as-prepared CsSnX3 perovskite NW arrays decrease from 1.84 to 1.34 eV with X changes from Br to I. The high crystallinity is confirmed by the strong photoluminescence (PL) emission peaks and uniform two-dimensional PL mapping images. In the end, the as-prepared high-quality CsSnI3 perovskite NW array is then configured into a near-infrared photodetector for the first time, exhibiting fast rise and decay time constants of 83.8 and 243.4 ms, respectively. All of the results present an important advance in the field of low-dimensional all-inorganic perovskites

Multiphoton excited singlet/triplet mixed self-trapped exciton emission.

Acknowledgements: This work was supported by the National Natural Science Foundation of China (Grant Nos. 62075198, 11974317, 12274378), Outstanding Youth Foundation of Henan (Grant Nos. 222300420087).Multiphoton excited luminescence is of paramount importance in the field of optical detection and biological photonics. Self-trapped exciton (STE) emission with self-absorption-free advantages provide a choice for multiphoton excited luminescence. Herein, multiphoton excited singlet/triplet mixed STE emission with a large full width at half-maximum (617 meV) and Stokes shift (1.29 eV) has been demonstrated in single-crystalline ZnO nanocrystals. Temperature dependent steady state, transient state and time-resolved electron spin resonance spectra demonstrate a mixture of singlet (63%) and triplet (37%) mixed STE emission, which contributes to a high photoluminescence quantum yield (60.5%). First-principles calculations suggest 48.34 meV energy per exciton stored by phonons in the distorted lattice of excited states, and 58 meV singlet-triplet splitting energy for the nanocrystals being consistent with the experimental measurements. The model clarifies long and controversial debates on ZnO emission in visible region, and the multiphoton excited singlet/triplet mixed STE emission is also observed

Multiphoton excited singlet/triplet mixed self-trapped exciton emission.

Multiphoton excited luminescence is of paramount importance in the field of optical detection and biological photonics. Self-trapped exciton (STE) emission with self-absorption-free advantages provide a choice for multiphoton excited luminescence. Herein, multiphoton excited singlet/triplet mixed STE emission with a large full width at half-maximum (617 meV) and Stokes shift (1.29 eV) has been demonstrated in single-crystalline ZnO nanocrystals. Temperature dependent steady state, transient state and time-resolved electron spin resonance spectra demonstrate a mixture of singlet (63%) and triplet (37%) mixed STE emission, which contributes to a high photoluminescence quantum yield (60.5%). First-principles calculations suggest 48.34 meV energy per exciton stored by phonons in the distorted lattice of excited states, and 58 meV singlet-triplet splitting energy for the nanocrystals being consistent with the experimental measurements. The model clarifies long and controversial debates on ZnO emission in visible region, and the multiphoton excited singlet/triplet mixed STE emission is also observed