Histamine deficiency delays ischaemic skeletal muscle regeneration via inducing aberrant inflammatory responses and repressing myoblast proliferation

Abstract

Histidine decarboxylase (HDC) catalyses the formation of histamine from L‐histidine. Histamine is a biogenic amine involved in many physiological and pathological processes, but its role in the regeneration of skeletal muscles has not been thoroughly clarified. Here, using a murine model of hindlimb ischaemia, we show that histamine deficiency in Hdc knockout (Hdc−/−) mice significantly reduces blood perfusion and impairs muscle regeneration. Using Hdc‐EGFP transgenic mice, we demonstrate that HDC is expressed predominately in CD11b+Gr‐1+ myeloid cells but not in skeletal muscles and endothelial cells. Large amounts of HDC‐expressing CD11b+ myeloid cells are rapidly recruited to injured and inflamed muscles. Hdc−/− enhances inflammatory responses and inhibits macrophage differentiation. Mechanically, we demonstrate that histamine deficiency decreases IGF‐1 (insulin‐like growth factor 1) levels and diminishes myoblast proliferation via H3R/PI3K/AKT‐dependent signalling. These results indicate a novel role for HDC‐expressing CD11b+ myeloid cells and histamine in myoblast proliferation and skeletal muscle regeneration.

Histamine Signaling Is Essential for Tissue Macrophage Differentiation and Suppression of Bacterial Overgrowth in the Stomach

“…HDC deficiency led to the accumulation of CD11b þ Ly6G þ immature myeloid cells, 6 and inhibited CD8 þ T-cell proliferation. 7 The histamine signal also promotes the differentiation of macrophages 8,9 and monocyte-derived dendritic cells. 10 Furthermore, the H 2 -receptor-mediated signal was shown to be pivotal for the maintenance of myeloid-biased hematopoietic stem cells 11 and the differentiation of human monocyte-derived M1 macrophages, 12 suggesting a potential role of disrupted histamine signaling-mediated immunologic disorders in the development of hypertrophic gastropathy in HDC-deficient mice.…”

Role of histamine-mediated macrophage differentiation in clearance of metastatic bacterial infection

“…Histamine is an organic molecule based on the ammonia (NH 3 ) structure, which plays various biological roles such as in the regulation of immune responses ( 17 ), neurotransmission ( 18 ), and gastric acid secretion ( 19 ). In the innate immune system, histamine signaling is a primary factor in the allergic responses by mast cells, and further promotes the differentiation of macrophages ( 20 , 21 ), monocyte-derived dendritic cells (DCs) ( 22 ), hematopoietic stem cells ( 23 ), and human M1-type macrophages ( 24 ). Endogenous histamine is generated through the decarboxylation of histidine by histidine decarboxylase (HDC) ( 25 ).…”

l-Anserine Increases Muscle Differentiation and Muscle Contractility in Human Skeletal Muscle Cells

“…24 Abudupataer et al have reported that histamine acts on myoblast proliferation and muscle regeneration in histidine decarboxylase-knockout mice. 33 These findings suggest that Lanserine increases the contractile force of skeletal muscle via H1R. On the other hand, the L-anserine-induced increase in muscle contractility was not affected by the addition of H2R or H3R antagonists (Figure 5).…”

“…Gurel et al have reported that histamine improves muscle strength in mdx mice . Abudupataer et al have reported that histamine acts on myoblast proliferation and muscle regeneration in histidine decarboxylase-knockout mice . These findings suggest that l -anserine increases the contractile force of skeletal muscle via H1R.…”