Anti-C1QTNF6 monoclonal antibody Made to order

C1qTNF-Related proteins (CTRPs), a new highly conserved family of adiponectin paralogs, were recently identified as being involved in diverse processes including metabolism, host defense, apoptosis, cell differentiation, and organogenesis. However, the functional role of CTRP6 remains poorly identified. Here we provide evidence that CTRP6 induces the expression of interleukin-10 (IL-10) in macrophages. Conditioned medium from CTRP6-expressing HEK293 cells increased IL-10 expression in Raw264.7 cells. The globular domain of CTRP6 (gCTRP6) also dose-dependently increased both IL-10 mRNA and protein expression levels, with transcript levels increasing within 2 h. Furthermore, the globular domain of CTRP6 rapidly induced phosphorylation of ERK1/2 in Raw264.7 cells. Treatment with U0126, a selective inhibitor, abolished CTRP6-stimulated IL-10 induction. Taken together, there results demonstrate that CTRP6 induces expression of IL-10 via ERK1/2 activation. Considering that IL-10 is a potent anti-inflammatory cytokine that modulates inflammatory signaling pathways, CTRP6 may be a novel target for pharmacological drugs in inflammatory diseases.

Intramuscular fat (IMF) and subcutaneous fat (SCF), which are modulated by adipogenesis of intramuscular and subcutaneous adipocytes, play key roles in pork quality. C1q/tumor necrosis factor-related protein 6 (CTRP6), an adipokine, plays an important role in the differentiation of 3T3-L1 cells. However, the effect and regulatory mechanisms of CTRP6 on porcine adipogenesis, and whether CTRP6 has the same effect on intramuscular and subcutaneous adipocytes, are still unknown. Here, we found that CTRP6 significantly inhibited both adipocyte proliferation assessed by proliferative marker expression, but CTRP6 decreased the proliferation rate of intramuscular adipocytes (IM) to a greater extent than subcutaneous adipocytes (SC). Moreover, CTRP6 promoted the activity of the p38 signaling pathway during the proliferation of both cell types. Nevertheless, in subcutaneous adipocytes, CTRP6 also influenced the phosphorylation of extracellular regulated protein kinases1/2 (p-Erk1/2), but not in intramuscular adipocytes. Additionally, during the differentiation of intramuscular and subcutaneous adipocytes, CTRP6 increased adipogenic genes expression and the level of p-p38, while it decreased the activity of p-Erk1/2. Interestingly, the effect of CTRP6 shRNA or CTRP6 recombinant protein was attenuated by U0126 (a special p-Erk inhibitor) or SB203580 (a special p-p38 inhibitor) in adipocytes. By target gene prediction and experimental validation, we demonstrated that CTRP6 may be a target of miR-29a in porcine adipocytes. Moreover, AdipoR1 was identified as a receptor of CTRP6 in intramuscular adipocytes, but not in subcutaneous adipocytes. On the basis of the above findings, we suggest that CTRP6 was the target gene of miR-29a, inhibited intramuscular and subcutaneous adipocyte proliferation, but promoted differentiation by the mitogen-activated protein kinase (MAPK) signaling pathway. These findings indicate that CTRP6 played an essentially regulatory role in fat development.