Open AccessHistamine deficiency delays ischaemic skeletal muscle regeneration via inducing aberrant inflammatory responses and repressing myoblast proliferation
Author(s) -
Abudupataer Mieradilijiang,
Zou Weihong,
Zhang Weiwei,
Ding Suling,
Zhou Zheliang,
Chen Jinmiao,
Li Hui,
Zhang Zhiwei,
Wang Chunsheng,
Ge Junbo,
Hong Tao,
Yang Xiangdong
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14720
Subject(s) - skeletal muscle , histidine decarboxylase , histamine , regeneration (biology) , pi3k/akt/mtor pathway , microbiology and biotechnology , myocyte , biology , endocrinology , inflammation , chemistry , myeloid , medicine , protein kinase b , cancer research , immunology , biochemistry , signal transduction , histidine , enzyme
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.