Human CNTF (Ciliary neurotrophic factor) ELISA Kit

The transition of differentiated Schwann cells to support of nerve repair after injury is accompanied by remodeling of the Schwann cell epigenome. The EED-containing polycomb repressive complex 2 (PRC2) catalyzes histone H3K27 methylation and represses key nerve repair genes such as Shh, Gdnf, and Bdnf, and their activation is accompanied by loss of H3K27 methylation. Analysis of nerve injury in mice with a Schwann cell-specific loss of EED showed the reversal of polycomb repression is required and a rate limiting step in the increased transcription of Neuregulin 1 (type I), which is required for efficient remyelination. However, mouse nerves with EED-deficient Schwann cells display slow axonal regeneration with significantly low expression of axon guidance genes, including Sema4f and Cntf. Finally, EED loss causes impaired Schwann cell proliferation after injury with significant induction of the Cdkn2a cell cycle inhibitor gene. Interestingly, PRC2 subunits and CDKN2A are commonly co-mutated in the transition from benign neurofibromas to malignant peripheral nerve sheath tumors (MPNST's). RNA-seq analysis of EED-deficient mice identified PRC2-regulated molecular pathways that may contribute to the transition to malignancy in neurofibromatosis.

The cytokines CLCF1 and CNTF are ligands for the CNTF receptor and the apolipoprotein E (ApoE) receptor sortilin. Both share structural similarities with the N-terminal domain of ApoE, known to bind CNTF. We therefore evaluated whether ApoE or ApoE-containing lipoproteins interact with CLCF1 and regulate its activity. We observed that CLCF1 forms complexes with the three major isoforms of ApoE in co-immunoprecipitation and proximity assays. FPLC analysis of mouse and human sera mixed with CLCF1 revealed that CLCF1 co-purifies with plasma lipoproteins. Studies with sera from ApoE(-/-)mice indicate that ApoE is not required for CLCF1-lipoprotein interactions. VLDL-and LDL-CLCF1 binding was confirmed using proximity and ligand blots assays. CLCF1-induced STAT3 phosphorylation was significantly reduced when the cytokine was complexed with VLDL. Physiological relevance of our findings was asserted in a mouse model of oxygen-induced retinopathy, where the beneficial antiangiogenic properties of CLCF1 were abrogated when co-administrated with VLDL, indicating, that CLCF1 binds purified lipoproteins or lipoproteins in physiological fluids such as serum and behave as a "lipocytokine". Albeit it is clear that lipoproteins modulate CLCF1 activity, it remains to be determined whether lipoprotein binding directly contributes to its neurotrophic function and its roles in metabolic regulation.