An antibody that inhibits TGF-β1 release from latent extracellular matrix complexes attenuates the progression of renal fibrosis.

Inhibitors of the transforming growth factor-β (TGF-β) pathway are potentially promising antifibrotic therapies, but nonselective simultaneous inhibition of all three TGF-β homologs has safety liabilities. TGF-β1 is noncovalently bound to a latency-associated peptide that is, in turn, covalently bound to different presenting molecules within large latent complexes. The latent TGF-β-binding proteins (LTBPs) present TGF-β1 in the extracellular matrix, and TGF-β1 is presented on immune cells by two transmembrane proteins, glycoprotein A repetitions predominant (GARP) and leucine-rich repeat protein 33 (LRRC33).

Click Chemistry Selectively Activates an Auristatin Protodrug with either Intratumoral or Systemic Tumor-Targeting Agents.

The Click Activated Protodrugs Against Cancer (CAPAC) platform enables the activation of powerful cancer drugs at tumors. CAPAC utilizes a click chemistry reaction between tetrazine and -cyclooctene. The reaction between activator, linked to a tumor-targeting agent, and protodrug leads to the targeted activation of the drug.

Mechanism Governing Human Kappa-Opioid Receptor Expression under Desferrioxamine-Induced Hypoxic Mimic Condition in Neuronal NMB Cells.

Cellular adaptation to hypoxia is a protective mechanism for neurons and relevant to cancer. Treatment with desferrioxamine (DFO) to induce hypoxia reduced the viability of human neuronal NMB cells. Surviving/attached cells exhibited profound increases of expression of the human kappa-opioid receptor (hKOR) and hypoxia inducible factor-1α (HIF-1α).

TGF-β regulates phosphorylation and stabilization of Sox9 protein in chondrocytes through p38 and Smad dependent mechanisms.

Members of the TGF-β superfamily are important regulators of chondrocyte function. Sox9, a key transcriptional regulator of chondrogenesis, is required for TGF-β-mediated regulation of specific cartilage genes. TGF-β can signal through a canonical, Smad-mediated pathway or non-conical pathways, including p38.

Cystic fibrosis transmembrane conductance regulator activation by roflumilast contributes to therapeutic benefit in chronic bronchitis.

Cigarette smoking causes acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction and is associated with delayed mucociliary clearance and chronic bronchitis. Roflumilast is a clinically approved phosphodiesterase 4 inhibitor that improves lung function in patients with chronic bronchitis. We hypothesized that its therapeutic benefit was related in part to activation of CFTR.

Inactivation of Tgfbr2 in Osterix-Cre expressing dental mesenchyme disrupts molar root formation.

It has been difficult to examine the role of TGF-ß in post-natal tooth development due to perinatal lethality in many of the signaling deficient mouse models. To address the role of Tgfbr2 in postnatal tooth development, we generated a mouse in which Tgfbr2 was deleted in odontoblast- and bone-producing mesenchyme. Osx-Cre;Tgfbr2(fl/fl) mice were generated (Tgfbr2(cko)) and post-natal tooth development was compared in Tgfbr2(cko) and control littermates.