Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Floral color polymorphism can provide great insight into species evolution from a genetic and ecological standpoint. Color variations between species are often mediated by pollinators and are fixed characteristics, indicating their relevance to adaptive evolution, especially between plants within a single population or between similar species. The orchid genus Pleione has a wide variety of flower colors, from violet, rose-purple, pink, to white, but their color formation and its evolutionary mechanism are unclear. Here, we selected the P. limprichtii population in Huanglong, Sichuan Province, China, which displayed three color variations: Rose-purple, pink, and white, providing ideal material for exploring color variations with regard to species evolution. We investigated the distribution pattern of the different color morphs. The ratio of rose-purple:pink:white-flowered individuals was close to 6:3:1. We inferred that the distribution pattern may serve as a reproductive strategy to maintain the population size. Metabolome analysis was used to reveal that cyanindin derivatives and delphidin are the main color pigments involved. RNA sequencing was used to characterize anthocyanin biosynthetic pathway-related genes and reveal different color formation pathways and transcription factors in order to identify differentially-expressed genes and explore their relationship with color formation. In addition, qRT-PCR was used to validate the expression patterns of some of the genes. The results show that PlFLS serves as a crucial gene that contributes to white color formation and that PlANS and PlUFGT are related to the accumulation of anthocyanin which is responsible for color intensity, especially in pigmented flowers. Phylogenetic and co-expression analyses also identified a R2R3-MYB gene PlMYB10, which is predicted to combine with PlbHLH20 or PlbHLH26 along with PlWD40-1 to form an MBW protein complex (MYB, bHLH, and WDR) that regulates PlFLS expression and may serve as a repressor of anthocyanin accumulation-controlled color variations. Our results not only explain the molecular mechanism of color variation in P. limprichtii, but also contribute to the exploration of a flower color evolutionary model in Pleione, as well as other flowering plants.

Chronic Aristolochic Acid Nephropathy (AAN) is a progressive chronic kidney disease related to herb medicine. However, treatment for chronic AAN remains ineffective. We report here that Smad7 is protective and has therapeutic potential for chronic AAN. In a mouse model of chronic AAN, progressive renal injury was associated with a loss of renal Smad7 and disruption of Smad7 largely aggravated the severity of chronic AAN as demonstrated by a significant increase in levels of 24-hour urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation. In contrast, restored Smad7 locally in the kidneys of Smad7 knockout mice prevented the progression of chronic AAN. Further studies revealed that worsen chronic AAN in Smad7 knockout mice was associated with enhanced activation of TGF-β/Smad3 and NF-κB signaling pathways, which was reversed when renal Smad7 was restored. Importantly, we also found that overexpression of Smad7 locally in the kidneys with established chronic AAN was capable of attenuating progressive chronic AAN by inactivating TGF-β/Smad3-medated renal fibrosis and NF-κB-driven renal inflammation. In conclusion, Smad7 plays a protective role in the pathogenesis of chronic AAN and overexpression of Smad7 may represent a novel therapeutic potential for chronic AAN.