p38 MAPK in Epithelial-Mesenchymal Transition Figure 2. Inverted microscope analysis of the HK-2 cells cultured under different conditions. (A) A typical epithelial cuboidal shape of the HK-2 cells cultured in 5.5 mM glucose condition were shown, with the characteristic cobblestone morphology. (B–C)Morphological changes of the HK-2 cells. The cells became more elongated, less adhered and lost their apical-to-basal polarity after treated with 30 mM glucose(B) or 30 mM glucose+Cont siRNA(C).(D–F)Changes of the cells were reversed, which were exposed to 30 mM glucose+p38 siRNA for 24 h(D) or for 48 h(E) or 30 mM glucose+AP-1 inhibitor(F). doi:10.1371/journal.pone.0022806.g002 Effect of p38 MAPK on fibronectin synthesis in HK-2 cells Fibronectin is a high-molecular-weight extracellular matrix glycoprotein that binds to membrane-spanning receptor proteins and therefore plays a major role in cell adhesion, growth, migration and differentiation. Fibronectin is also central to the processes of wound healing and embryonic development. We Figure 3. Transmission electron microscopic analysis of the HK-2 cells cultured under different conditions. (A–C)The HK-2 cells under 30 mM glucose (B) or 30 mM glucose+Cont siRNA (C) showed decreased number of microvilli, mitochondria and increased volume density of rough endoplasmic reticulum compared to that of the cells cultured in 5.5 mM glucose(A). (D–F)Changes of the cells were reversed,which were cultured in the 30 mM glucose+p38 siRNA for 24 h(D) or 48 h(E) or 30 mM glucose+AP-1 inhibitor(F). doi:10.1371/journal.pone.0022806.g003 PLoS ONE | www.plosone.org 3 July 2011 | Volume 6 | Issue 7 | e22806