ASK1-dependent recruitment and activation of macrophages induce hair growth in skin wounds

Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein 3-kinase family that activates both c-Jun NH2-terminal kinase and p38 pathways in response to inflammatory cytokines and physicochemical stress. We report that ASK1 deficiency in mice results in dramatic retardation of wounding-induced hair regrowth in skin. Oligonucleotide microarray analysis revealed that expression of several chemotactic and activating factors for macrophages, as well as several macrophage-specific marker genes, was reduced in the skin wound area of ASK1-deficient mice. Intracutaneous transplantation of cytokine-activated bone marrow-derived macrophages strongly induced hair growth in both wild-type and ASK1-deficient mice. These findings indicate that ASK1 is required for wounding-induced infiltration and activation of macrophages, which play central roles in inflammation-dependent hair regrowth in skin

Collision Tumor of Adenocarcinoma and Gastrointestinal Stromal Tumor in the Small Bowel

We report a very rare case of collision tumor composed of primary adenocarcinoma of the jejunum and gastrointestinal stromal tumor (GIST). The patient was a 63-year-old man who visited our hospital for epigastralgia and vomiting. Abdominal computed tomography revealed a mass in the upper jejunum, with gastric and duodenal dilatation. Endoscopy of the small bowel showed a circumferential tumor in the upper jejunum, which was diagnosed as primary adenocarcinoma by tissue biopsy. Thereafter, partial resection of the small bowel from the third part of the duodenum over the upper jejunum was performed. A tumor colliding with the primary adenocarcinoma was identified on the serosal side of the jejunum in the excised specimen and was histologically diagnosed as GIST. The annual incidence of primary adenocarcinoma of the small bowel (i.e., jejunum and ileum excluding the duodenum) has been reported to be 7 in 1 million people, and only 6 cases of collision tumor of the small bowel (i.e., duodenum: 5, ileum: 1) have been reported thus far. Although esophageal, gastric, and large intestinal collision tumors composed of primary cancer and GIST have been reported, to our knowledge, the present patient is the first case of the small bowel. The cause of or correlation between 2 tumors forming a collision tumor remains unclear. In the present patient, there was no pathological finding of infiltration between the 2 tumors. Although the collision of the 2 tumors was unclear, the findings indicate their independent development in closely located regions consistent with collision tumors

Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.

Histone H3 lysine-9 di-methylation (H3K9me2) and lysine-27 tri-methylation (H3K27me3) are linked to repression of gene expression, but the functions of repressive histone methylation dynamics during inflammatory responses remain enigmatic. Here, we report that lysine demethylases 7A (KDM7A) and 6A (UTX) play crucial roles in tumor necrosis factor (TNF)-α signaling in endothelial cells (ECs), where they are regulated by a novel TNF-α-responsive microRNA, miR-3679-5p. TNF-α rapidly induces co-occupancy of KDM7A and UTX at nuclear factor kappa-B (NF-κB)-associated elements in human ECs. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and are both required for activation of NF-κB-dependent inflammatory genes. Chromosome conformation capture-based methods furthermore uncover increased interactions between TNF-α-induced super enhancers at NF-κB-relevant loci, coinciding with KDM7A and UTX recruitments. Simultaneous pharmacological inhibition of KDM7A and UTX significantly reduces leukocyte adhesion in mice, establishing the biological and potential translational relevance of this mechanism. Collectively, these findings suggest that rapid erasure of repressive histone marks by KDM7A and UTX is essential for NF-κB-dependent regulation of genes that control inflammatory responses of ECs