Vladimir N. Simirskii

CD44 expression is developmentally regulated in the mouse lens and increases in the lens epithelium after injury.

Hyaluronan is an oligosaccharide found in the pericellular matrix of numerous cell types and hyaluronan-induced signaling is known to facilitate fibrosis and cancer progression in some tissues. Hyaluronan is also commonly instilled into the eye during cataract surgery to protect the corneal endothelium from damage. Despite this, little is known about the distribution of hyaluronan or its receptors in the normal ocular lens. In this study, hyaluronan was found throughout the mouse lens, with apparently higher concentrations in the lens epithelium. CD44, a major cellular receptor for hyaluronan, is expressed predominately in mouse secondary lens fiber cells born from late embryogenesis into adulthood. Surgical removal of lens fiber cells from adult mice resulted in a robust upregulation of CD44 protein, which preceded the upregulation of alpha-smooth muscle actin expression typically used as a marker of epithelial-mesenchyma transition in this model of lens epithelial cell fibrosis. Mice lacking the CD44 gene had morphologically normal lenses with a response to lens fiber cell removal similar to wildtype, although they exhibited an increase in cell-associated hyaluronan. Overall, these data suggest that lens cells have a hyaluronan-containing pericellular matrix whose structure is partially regulated by CD44. Further, these data indicate that CD44 upregulation in the lens epithelium may be an earlier marker of lens injury responses in the mouse lens than the upregulation of alpha-smooth muscle actin.

Role of Protein Kinase Cα in Regulation of [Ca2+]I and Force in Human Myometrium

Recent findings implicate protein kinase C in regulation of contraction of uterine muscle (myometrium). However, the role of protein kinase C isoforms in myometrial contraction remains uncertain. Therefore, this study examined protein kinase Cαs role in regulation of contraction and intracellular calcium concentration ([Ca2+]I) of myometrium from term pregnant women. The authors demonstrated that protein kinase Cα inhibitor Go6976 decreased the amplitude of potassium chloride—induced myometrial contractions in a time-dependent manner. The treatment of the myometrial strips with protein kinase Cα—specific antisense oligodeoxynucleotides decreased the potassium chloride—induced contraction and [Ca2+]I response to 39.3% + 6.8% and 50.0% + 3.3%, respectively, compared to control. The sense oligonucleotides treatment did not significantly change the potassium chloride responses (89.8% + 6.8% and 93.9% + 4.5% of the control for the contraction and [Ca2+]I, respectively). These data, coupled with the observation that protein kinase Cα levels are elevated in the pregnant myometrium, suggest the involvement of protein kinase Cα in regulation of human uterine contraction.

β1-integrin controls cell fate specification in early lens development.

Integrins are heterodimeric cell surface molecules that mediate cell-extracellular matrix (ECM) adhesion, ECM assembly, and regulation of both ECM and growth factor induced signaling. However, the developmental context of these diverse functions is not clear. Loss of β1-integrin from the lens vesicle (mouse E10.5) results in abnormal exit of anterior lens epithelial cells (LECs) from the cell cycle and their aberrant elongation toward the presumptive cornea by E12.5. These cells lose expression of LEC markers and initiate expression of the Maf (also known as c-Maf) and Prox1 transcription factors as well as other lens fiber cell markers. β1-integrin null LECs also upregulate the ERK, AKT and Smad1/5/8 phosphorylation indicative of BMP and FGF signaling. By E14.5, β1-integrin null lenses have undergone a complete conversion of all lens epithelial cells into fiber cells. These data suggest that shortly after lens vesicle closure, β1-integrin blocks inappropriate differentiation of the lens epithelium into fibers, potentially by inhibiting BMP and/or FGF receptor activation. Thus, β1-integrin has an important role in fine-tuning the response of the early lens to the gradient of growth factors that regulate lens fiber cell differentiation.