The Role of the p38 MAPK Signaling Pathway in High Glucose-Induced Epithelial-Mesenchymal Transition of Cultured Human Renal Tubular Epithelial Cells

Epithelial-mesenchymal transition of tubular epithelial cells, which is characterized by a loss of epithelial cell characteristics and a gain of ECM-producing myofibroblast characteristics, is an essential mechanism that is involved in tubulointerstitial fibrosis, an important component of the renal injury that is associated with diabetic nephropathy. Under diabetic conditions, p38 MAPK activation has been reported in glomeruli and mesangial cells; however, studies on p38 MAPK in TECs are lacking. In this study, the role of p38 MAPK in AP-1 activation and in the EMT in the human proximal tubular epithelial cell line (HK-2) under high glucose concentration conditions is investigated.A vector for small interfering RNA that targets p38 MAPK was constructed; the cells were then either transfected with p38 siRNA or pretreated with a chemical inhibitor of AP-1 and incubated with low glucose plus TGF-β1 or high glucose for 48 h. Cells that were not transfected or pretreated and were exposed to low glucose with or without TGF-β1 or high glucose for 48 h were considered to be the controls. We found that high glucose induced an increase in TGF-β1. And high glucose-induced p38 MAPK activation was inhibited by p38 siRNA (P<0.05). A significant decline in E-cadherin and CK expression and a notable increase in vimentin and α-SMA were detected when exposed to low glucose with TGF-β1 or high glucose, and a significant raise of secreted fibronectin were detected when exposed to high glucose; whereas these changes were reversed when the cells were treated with p38 siRNA or AP-1 inhibitor (P<0.05). AP-1 activity levels and Snail expression were up-regulated under high glucose conditions but were markedly down-regulated through knockdown of p38 MAPK with p38 siRNA or pretreatment with AP-1 inhibitor (P<0.05).This study suggests that p38 MAPK may play an important role in the high glucose-induced EMT by activating AP-1 in tubular epithelial cells

Evolvability in the Cephalothoracic Structural Complexity of Aegla araucaniensis (Crustacea: Decapoda) Determined by a Developmental System with Low Covariational Constraint

The integration of complex structures is proportional to the intensity of the structural fusion; its consequences are better known than the covariational effects under less restrictive mechanisms. The synthesis of a palimpsest model based on two early parallel pathways and a later direct pathway explains the cephalothoracic complexity of decapod crustaceans. Using this model, we tested the evolvability of the developmental modularity in Aegla araucaniensis, an anomuran crab with an evident adaptive sexual dimorphism. The asymmetric patterns found on the landmark configurations suggest independent perturbations of the parallel pathways in each module and a stable asymmetry variance near the fusion by canalization of the direct pathway, which was more intense in males. The greater covariational flexibility imposed by the parallel pathways promotes the expression of gonadic modularity that favors the reproductive output in females and agonistic modularity that contributes to mating success in males. Under these divergent expressions of evolvability, the smaller difference between developmental modularity and agonistic modularity in males suggests higher levels of canalization due to a relatively more intense structural fusion. We conclude that: (1) the cephalothorax of A. araucaniensis is an evolvable structure, where parallel pathways promote sexual disruptions in the expressions of functional modularity, which are more restricted in males, and (2) the cephalothoracic palimpsest of decapods has empirical advantages in studying the developmental causes of evolution of complex structures