Apart from soluble growth factors, various other biophysicochemical cues are known to promote chondrogenesis. Under physiological conditions, cartilage in the joint comprises a hyperosmotic and hypoxic environment. Therefore, in this study, we examined the inductive effects of hyperosmotic and/or hypoxic conditions on adipose stem cells (ASCs) and compared them with conventional TGFβ1-induction...

OBJECTIVES Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. While breastfeeding is known to impact neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated three essential breast milk cytokines and ...

Lack or downregulation of the dopamine D2 receptor (D2R) increases the vulnerability to renal inflammation independent of blood pressure in mice. Common single nucleotide polymorphisms (SNPs) rs6276, 6277, and 1800497 in the human D2R gene are associated with decreased receptor expression/function and hypertension. Human renal proximal tubule cells from subjects carrying these SNPs have decreas...

BACKGROUND Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis. The etiology is unclear, but genetic predisposition may be a contributing factor. We used adenovirus-mediated gene transfer of transforming growth factor (TGF) β1 to the peritoneum in four genetically distinct laboratory mouse strains to assess differences in fibrogenic response. ...

Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleter...

The serum-and-glucocorticoid-inducible-kinase-1 (SGK1) is ubiquitously expressed and under genomic control by cell stress, hormones and further mediators. A most powerful stimulator of SGK1 expression is transforming growth factor TGFβ1. SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase and the 3-phosphoinositide-dependent kinase PDK1. As shown recently, SGK1 inc...

Renal fibrosis is a serious clinical problem resulting in the greatest need for renal replacement therapy. No adequate preventive or curative therapy is available that could be clinically used to target renal fibrosis specifically. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the under...

PGE2 exerts its biological effect through binding to various EP receptors that result inactivation of various signal transduction pathways. It also plays an important role in mice glomerular mesangial cells (MCs) damage induced by transforming growth factor-β1 (TGF-β1); however, the molecular mechanisms remain unknown. In the present study, we tested the efficacy of four selective agonists of P...

Epithelial to mesenchymal transition (EMT) and pulmonary fibrogenesis require epithelial integrin α3β1-mediated cross-talk between TGFβ1 and Wnt signaling pathways. One hallmark of this cross-talk is pY654-β-catenin accumulation, but whether pY654-β-catenin is a biomarker of fibrogenesis or functionally important is unknown. To clarify further the role of β-catenin in fibrosis, we explored pY65...

BACKGROUND The TGF-β signaling pathway is an essential regulator of many cellular process involved in carcinogenesis. Smad proteins are central to the function of TGF-β signaling. In this study, we evaluated genetic variation in TGFβ1, TGFβR1, Smad1, Smad2, Smad3, and Smad4 and risk of colon and rectal cancer. METHODS Data are from a large case-control study of colon (n = 1,444 cases, 1,841 c...