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Our previous study indicated that streptozotocin (STZ)‐induced diabetes leads to colonic platelet‐derived growth factor receptor‐α‐positive (PDGFRα+) cell proliferation accompanied by slow colonic transit in mice; however, the mechanism of this effect is unclear. The present study used western blotting, immunohistochemistry, and quantitative PCR to investigate whether proteinase‐activated receptor 2 (PAR2) mediates PDGFRα+ cell proliferation. Our results showed that PDGFRα, PAR2, and Ki‐67 coexpression was increased in the diabetic colonic muscle layer. PDGFRα and PAR2 mRNA and protein expression levels were also markedly enhanced in the diabetic colonic muscle layer. Mice treated with 2‐furoyl‐LIGRLO‐amide (2‐F‐L‐a), a PAR2 agonist, exhibited significant colon elongation and increased smooth muscle weight. In the 2‐F‐L‐a‐treated mice, PDGFRα, PAR2, and Ki‐67 coexpression was increased and PDGFRα and PAR2 mRNA and protein expression was significantly enhanced in the colonic smooth muscle layer. 2‐F‐L‐a also increased proliferation and PDGFRα expression in NIH/3T3 cells cultured in high glucose, while LY294002, a PI3K antagonist, decreased cell proliferation and PDGFRα expression. PI3K and Akt protein and mRNA expression and p‐Akt protein expression in diabetic and 2‐F‐L‐a‐treated mice were markedly reduced in colonic smooth muscle. 2‐F‐L‐a also reduced PI3K, Akt, and p‐Akt protein expression in NIH/3T3 cells, while the PI3K antagonist LY294002 increased this expression. The results indicate that PAR2 is involved in the proliferation of PDGFRα+ cells through the PI3K/Akt signaling pathway in the colon of STZ‐induced diabetic mice, which may contribute to the slow transit and constipation that are associated with diabetes. [ABSTRACT FROM AUTHOR]

Background and Purpose Emerging evidence indicates that stimulating adult neurogenesis provides novel strategies for central nervous system diseases. Iptakalim ( Ipt), a novel ATP-sensitive potassium (K- ATP) channel opener, has been demonstrated to play multipotential neuroprotective effects in vivo and in vitro. However, it remains unknown whether Ipt could regulate the adult neurogenesis. Methods and Results Based on the finding that adult neural stem cells ( ANSCs) in hippocampus expressed Kir6.1/ SUR1-composed K- ATP channel, Kir6.1 heterozygotic ( Kir6.1+/−) mice were used to investigate whether and how Ipt regulates adult hippocampal neurogenesis. We showed that administration of Ipt (10 mg/kg) or fluoxetine ( Flx, 10 mg/kg) for 4 weeks significantly increased newborn ANSCs in subgranular zone ( SGZ) of Kir6.1+/+ mice but failed to affect those of Kir6.1+/− mice. Meanwhile, ANSCs in Kir6.1+/− mice exhibited decreased survival rate and impaired ability of differentiation into astrocytes. We further found that Kir6.1+/− mice showed lower level of brain-derived neurotrophic factor ( BDNF) in hippocampus compared with Kir6.1+/+ mice. Furthermore, Ipt increased the levels of BDNF and basic fibroblast growth factor ( FGF-2) throughout the hippocampus in Kir6.1+/+ mice but not in Kir6.1+/− mice. Moreover, Ipt and Flx enhanced the phosphorylation of Akt and CREB in the hippocampus of Kir6.1+/+ mice. Notably, these effects were completely abolished in Kir6.1+/− mice. Conclusions Our findings demonstrate that Ipt stimulates the adult hippocampal neurogenesis via activation of Akt and CREB signal following the opening of Kir6.1-composed K- ATP channels, which gives us an insight into the therapeutic implication of Ipt in the diseases with adult neurogenesis deficiency, such as major depression. [ABSTRACT FROM AUTHOR]

The hetN gene plays an important role in heterocyst differentiation and pattern formation. An immunoblotting study showed that the hetN gene in Anabaena sp. PCC 7120 was expressed in vegetative cells grown with combined nitrogen. After a switch to a medium without combined nitrogen, hetN expression first declined and was then followed by a rapid increase in its product, HetN, which was only present in mature heterocysts. HetN is located on both thylakoid membranes and plasma membranes as determined by immunoblotting using purified membranes. Overexpression of hetN completely prevented hetR up-regulation under nitrogen-deprivation conditions, suggesting that its role in pattern control may depend on its inhibition of hetR expression. [Copyright &y& Elsevier]