Transcriptomic comparison of ovarian granulosa cells between adult sheep and prepubertal lambs

Background The oocyte development ability of prepubertal animals is significantly lower than that of adult animals. Granulosa cells (GCs) have an important function on regulation of follicular and oocyte development. Therefore, analysis of GCs characteristics can be used to explore the developmental mechanism of follicles and oocytes. Results In order to understand the possible reasons for the differences in follicles and oocytes development between lambs and adult sheep, we utilized high-throughput sequencing technique to analyze the transcriptome of GCs from follicle-stimulating hormone (FSH) superstimulated adult ewes and prepubertal lambs. Adult ewes were stimulated with FSH for 3 days (group A) and lambs were FSH-stimulated for 2 days (group B) or 3 days (group C). Transcriptome analysis of GCs showed that there were 405 and 159 differentially expressed genes from A vs. B and A vs. C, respectively. The results indicated that prolonging the FSH-stimulation of lambs made the GC state of lambs more similar to the adult sheep, but there were still a large number of differentially expressed genes between adult sheep and lambs. Further analysis showed that many differently expressed genes were implicated in cell proliferation and apoptosis, oocyte development and follicular ovulation. Cellular examination demonstrated that fatty acid binding protein 4 (FABP4), which was highly expressed in lamb GCs, had a potential of promoting cell apoptosis. Cytoplasmic phospholipase A2 (PLA2G4A), which was expressed lowly in lamb GCs, may be responsible for reduced synthesis of prostaglandins in cells and impaired follicle/oocyte development. In contrast, glutathione S-transferase β-1 (GSTT2B) and forkhead boxO6 (FOXO6) had no apparent effect on the proliferation and apoptosis of GCs.

Brusatol Derivative–34 Attenuates Allergic Airway Inflammation Via Inhibition of the Spleen Tyrosine Kinase Pathway

Brusatol derivative-34 (Bru-34), a derivative of brusatol, has been shown significantly anti-inflammatory activity in mice in our previously work. However, to our knowledge, there were very limited studies on how Bru-34 affected airway inflammation. Thus, in this present study, the effects and potential mechanisms of Bru-34 on allergic airway inflammation were examined both in vivo and in vitro. The results showed that Bru-34 attenuated the allergic airway inflammation in mice, with significant decreasing of the inflammatory cells and mediators in bronchoalveolar lavage fluids and attenuation of the histopathological alterations in the lung tissues. In addition, Bru-34 significantly inhibited the release of inflammatory cytokines in antigen induced rat basophilic leukemia -2H3 (RBL-2H3) cells. What’s more, Bru-34 significantly decreased the expression of spleen tyrosine kinase (Syk), p-Syk, cytoplasmic phospholipase A2 (cPLA2), p-cPLA2, nuclear factor-κB (NF-κB) and p-NF-κB both in allergic mice lung tissue and antigen induced RBL-2H3 cells. Furthermore, the collaborative effects of Bru-34 with inhibitors against Syk, cPLA2, and NF-κB, showed that Syk was an important target of Bru-34, and cPLA2 and NF-κB played important roles in the coordinated inflammatory response. In conclusion, Bru-34 could significantly modulate the allergic airway inflammation, and its potential mechanism was revealed at least partially via down-regulating of Syk-cPLA2 -NF-κB signaling.