The mechanism by which transforming growth factor-β (TGFβ) regulates differentiation in human epidermal keratinocytes is still poorly understood. To assess the role of Smad signaling, we engineered human HaCaT keratinocytes either expressing small interfering RNA against Smads2, 3, and 4 or overexpressing Smad7 and verified impaired Smad signaling as decreased Smad phosphorylation, aberrant nuc...

Background & Aims: Today, diabetic nephropathy is considered to be one of the most common causes of end stage renal disease. Uncontrolled hyperglycemia, and consequently, production of advanced glycation end products activate pathways which play key roles in diabetic nephropathy. Among these pathways, high expression of receptor for advanced glycation end products (RAGE) and transforming growth...

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Despite recent advances in the development of targeted therapies, patients with advanced disease remain incurable, mostly because metastatic non-small cell lung carcinomas (NSCLC) eventually become resistant to tyrosine kinase inhibitors (TKIs). Kinase inhibitors have the potential for target promiscuit...

Chronic human immunodeficiency virus and simian immunodeficiency virus (HIV and SIV) infections are characterized by mucosal inflammation in the presence of anti-inflammatory cytokines such as transforming growth factor β (TGFβ). The mechanisms for refractiveness to TGFβ are not clear. Here we show that the expression of microRNA miR-155 was significantly upregulated in the oropharyngeal mucosa...

Biomechanical signals play an important role in normal disc metabolism and pathology. For instance, nucleus pulposus (NP) cells will regulate metabolic activities and maintain a balance between the anabolic and catabolic cascades. The former involves factors such as transforming growth factor-β (TGFβ) and mechanical stimuli, both of which are known to regulate matrix production through autocrin...

The transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis. In cancer, two distinctive behaviors of TGFβ have been reported as a tumor suppressor at early stage of the disease, and as a tumor promoter at later stages. The past decades, the dualistic role of TGFβ has garnered a lot of attention. As a result, cancer researchers' has been tasked to elucidate how TGFβ signaling ...

The cascade of phosphorylation is a pivotal event in transforming growth factor beta (TGFbeta) signaling. Reversible phosphorylation regulates fundamental aspects of cell activity. TGFbeta-induced Smad7 binds to type I receptor (TGFbeta type I receptor; TbetaRI) functioning as a receptor kinase antagonist. We found Smad7 interacts with growth arrest and DNA damage protein, GADD34, a regulatory ...