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Cilia-localized LKB1 Regulates Chemokine Signaling, Macrophage Recruitment, and Tissue Homeostasis in the Kidney
Abstract: Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells. We identify a complex of the ciliary kinase LKB1 and several ciliopathy-related proteins including NPHP1 and PKD1. At homeostasis, this ciliary module suppresses expression of the chemokine CCL2 in tubular epithelial cells. Deletion of LKB1 or PKD1 in mouse renal tubules elevates CCL2 expression in a cell-autonomous manner and results in peritubular accumulation of CCR2+ mononuclear phagocytes, promoting a ciliopathy phenotype. Our findings establish an epithelial organelle, the cilium, as a gatekeeper of tissue immune cell numbers. This represents an unexpected disease mechanism for renal ciliopathies and establishes a new model for how epithelial cells regulate immune cells to affect tissue homeostasis
Tuning the 3D Microenvironment of Reprogrammed Tubule Cells Enhances Biomimetic Modeling of Polycystic Kidney Disease
Abstract: Renal tubular cells frequently lose differentiation markers and physiological properties when propagated in conventional cell culture conditions. Embedding cells in 3D microenvironments or controlling their 3D assembly by bioprinting can enhance their physiological properties, which is beneficial for modeling diseases in vitro. A potential cellular source for modeling renal tubular physiology and kidney diseases in vitro are directly reprogrammed induced renal tubular epithelial cells (iRECs). iRECs were cultured in various biomaterials and as bioprinted tubular structures. They showed high compatibility with the embedding substrates and dispensing methods. The morphology of multic...
W Tungsten
The present supplement volume, A 7, is the first of a triad, A 5 to A 7, dealing with the chemical reactions of metallic tungsten. It describes the reactions with inorganic and organic compounds, except for formation reactions of organotungsten compounds. Volume A 6, to appear at the beginning of 1988, will cover the reactions of tungsten with metallic elements. Volume A 5, in preparation for 1988/89, will contain the reactions with nonmetallic elements and, in addition, cover the electrochemistry of tungsten. With the appearance of this last volume, the present knowledge of the chemistry of tungsten will be compiled in more than 1000 pages. In the Gmelin main volume on tungsten, published i...
The Philosopher's Index
Vols. for 1969- include a section of abstracts.
W Tungsten
The present supplement volume, A 7, is the first of a triad, A 5 to A 7, dealing with the chemical reactions of metallic tungsten. It describes the reactions with inorganic and organic compounds, except for formation reactions of organotungsten compounds. Volume A 6, to appear at the beginning of 1988, will cover the reactions of tungsten with metallic elements. Volume A 5, in preparation for 1988/89, will contain the reactions with nonmetallic elements and, in addition, cover the electrochemistry of tungsten. With the appearance of this last volume, the present knowledge of the chemistry of tungsten will be compiled in more than 1000 pages. In the Gmelin main volume on tungsten, published i...
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