Nitric oxide (NO) plays a central role in the control of vascular homeostasis. Adequate NO production stimulated by continuous laminar flow on the endothelial surface, so-called shear stress, prevents endothelial inflammation and development of endothelial dysfunction. Recently, a novel class of mechanosensitive transcription factors has been identified that in endothelial cells transfer shear ...

The VEGF receptor, FLK1, is essential for differentiation of the endothelial lineage and for embryonic vascular development. Using comparative genomics, we have identified conserved ETS and Krüppel-like factor (KLF) binding sites within the Flk1 enhancer. In transgenic studies, mutation of either site results in dramatic reduction of Flk1 reporter expression. Overexpression of KLF2 or the ETS t...

Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment...

T follicular helper (TFH) cells are gatekeepers of the humoral immune response. Without help from this CD4+ T cell subset, B cells cannot differentiate into high-affinity memory B cells and antibody-producing long-lived plasma cells which are the basis of protective immune responses. At the same time, dysregulated TFH cell responses are causative for many autoimmune disorders (reviewed in [1])....

Absence of shear stress due to disturbed blood flow at arterial bifurcations and curvatures leads to endothelial dysfunction and proinflammatory gene expression, ultimately resulting in atherogenesis. KLF2 has recently been implicated as a transcription factor involved in mediating the anti-inflammatory effects of flow. We investigated the effect of shear on basal and TNF-alpha-induced genomewi...

Pseudomonas aeruginosa is an important opportunistic pathogen which is capable of causing both acute and chronic infections in immunocompromised patients. Successful adaptation of the bacterium to its host environment relies on the ability of the organism to tightly regulate gene expression. RsmA, a small RNA-binding protein, controls the expression of a large number of virulence-related genes ...

In skeletal muscle differentiation, muscle-specific genes are regulated by two groups of transcription factors, the MyoD and MEF2 families, which work together to drive the differentiation process. Here, we show that ERK5 regulates muscle cell fusion through Klf transcription factors. The inhibition of ERK5 activity suppresses muscle cell fusion with minimal effects on the expression of MyoD, M...

Diabetic retinopathy is one of the most common causes of blindness in North America. Several signaling mechanisms are activated secondary to hyperglycemia in diabetes, leading to activation of vasoactive factors. We investigated a novel pathway, namely extracellular signal regulated kinase 5 (ERK5) mediated signaling, in modulating glucose-induced vascular endothelial growth factor (VEGF) expre...

OBJECTIVE Endothelial transcription factors Krüppel-like factor 4 (KLF4) and KLF2 are implicated in protection against atherogenesis. Steady-state microRNA (miR) regulation of KLFs in vivo is accessible by screening region-specific endothelial miRs and their targets. METHODS AND RESULTS A subset of differentially expressed endothelial miRs was identified in atherosusceptible versus protected ...

UNLABELLED Although increased fetal hemoglobin (HbF) levels have proven benefit for people with β-hemoglobinopathies, all current HbF-inducing agents have limitations. We previously reported that drugs that activate the NRF2 antioxidant response signaling pathway increase HbF in primary human erythroid cells. In an attempt to increase HbF levels achieved with NRF2 activators, in the present stu...