Scarring of the kidney is a major public health concern, directly promoting loss of kidney function. In order to understand the role of microRNA (miRNA) in the progression of kidney scarring in response to injury, we investigated changes in miRNA expression in two kidney fibrosis models, and identified 24 commonly upregulated miRNAs. Among them, miR-21 was highly elevated in both animal models and human transplant kidney nephropathy. Deletion of miR-21 in mice resulted in no overt abnormality. However, miR-21-/- mice suffered far less interstitial fibrosis in response to kidney injury, which was pheno-copied in wild-type mice treated with anti-miR-21 oligonucleotides. Surprisingly, global de-repression of miR-21 target messenger RNAs was only readily detectable in miR-21-/- kidneys after injury. Analysis of gene expression profiles identified groups of genes involved in metabolic pathways that were up-regulated in the absence of miR-21, including the lipid metabolism pathway regulated by Peroxisome proliferator activated receptor-α (Pparα), a direct miR-21 target. Over-expression of Pparα prevented UUO-induced injury and fibrosis. Pparα deficiency abrogated the anti-fibrotic effect of anti-miR21 oligonucleotides. miR-21 also regulates the redox metabolic pathway. The mitochondrial inhibitor of reactive oxygen species generation, Mpv17l, was repressed by miR-21, correlating closely with enhanced oxidative kidney damage. These studies demonstrate that miR-21 contributes to fibrogenesis and epithelial injury in the kidney in two mouse models and is a candidate target for anti-fibrotic therapies.

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Lithium niobate (LN), an outstanding and versatile material, has influenced our daily life for decades: from enabling high-speed optical communications that form the backbone of the Internet to realizing radio-frequency filtering used in our cell phones. This half-century-old material is currently embracing a revolution in thin-film LN integrated photonics. The success of manufacturing wafer-scale, high-quality, thin films of LN on insulator (LNOI), accompanied with breakthroughs in nanofabrication techniques, have made high-performance integrated nanophotonic components possible. With rapid development in the past few years, some of these thin-film LN devices, such as optical modulators and nonlinear wavelength converters, have already outperformed their legacy counterparts realized in bulk LN crystals. Furthermore, the nanophotonic integration enabled ultra-low-loss resonators in LN, which unlocked many novel applications such as optical frequency combs and quantum transducers. In this Review, we cover-from basic principles to the state of the art-the diverse aspects of integrated thinfilm LN photonics, including the materials, basic passive components, and various active devices based on electro-optics, all-optical nonlinearities, and acousto-optics. We also identify challenges that this platform is currently facing and point out future opportunities. The field of integrated LNOI photonics is advancing rapidly and poised to make critical impacts on a broad range of applications in communication, signal processing, and quantum information.

Kidney pericytes are progenitors of scar-forming interstitial myofibroblasts that appear after injury. The function of kidney pericytes as microvascular cells and how these cells detach from peritubular capillaries and migrate to the interstitial space, however, are poorly understood. Here, we used an unbiased approach to identify genes in kidney pericytes relevant to detachment and differentiation in response to injury in vivo, with a particular focus on genes regulating proteolytic activity and angiogenesis. Kidney pericytes rapidly activated expression of a disintegrin and metalloprotease with thrombospondin motifs-1 (ADAMTS1) and downregulated its inhibitor, tissue inhibitor of metalloproteinase 3 (TIMP3) in response to injury. Similarly to brain pericytes, kidney pericytes bound to and stabilized capillary tube networks in three-dimensional gels and inhibited metalloproteolytic activity and angiogenic signaling in endothelial cells. In contrast, myofibroblasts did not have these vascular stabilizing functions despite their derivation from kidney pericytes. Pericyte-derived TIMP3 stabilized and ADAMTS1 destabilized the capillary tubular networks. Furthermore, mice deficient in Timp3 had a spontaneous microvascular phenotype in the kidney resulting from overactivated pericytes and were more susceptible to injury-stimulated microvascular rarefaction with an exuberant fibrotic response. Taken together, these data support functions for kidney pericytes in microvascular stability, highlight central roles for regulators of extracellular proteolytic activity in capillary homoeostasis, and identify ADAMTS1 as a marker of activation of kidney pericytes.