Abstract
Semaphorins are a family originally identified as axonal guidance molecules. They are also involved in tumor growth, angiogenesis, immune regulation, as well as other biological and pathological processes. Recent studies have shown that semaphorins play a role in metabolic diseases including obesity, adipose inflammation, and diabetic complications, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic wound healing, and diabetic osteoporosis. Evidence provides mechanistic insights regarding the role of semaphorins in metabolic diseases by regulating adipogenesis, hypothalamic melanocortin circuit, immune responses, and angiogenesis. In this review, we summarize recent progress regarding the role of semaphorins in obesity, adipose inflammation, and diabetic complications.
Highlights
Semaphorins are a large family of proteins involved in different physiological and pathological processes
We summarize the progress on the role of semaphorins in metabolic disorders including obesity, adipose inflammation, brown adipose tissue, immune cell metabolism, as well as diabetic complications
Sema6D is important for generation of intestinal resident CX3CR1hi macrophages and prevents development of colitis
Summary
Semaphorins are a large family of proteins involved in different physiological and pathological processes. In addition to the Sema domain, semaphorins contain the plexin-semaphorin-integrin (PSI) domain, and distinct protein domains that are expressed by different subclasses, including immunoglobulin-like (Ig), thrombospondin, and basic C-terminal domains [8]. Plexins, which are found in vertebrates and fall into Classes A–D, contain the extracellular Sema domains [11]. In addition to the Sema domain, like other semaphorin members, all Class-3 semaphorins contain at least two conserved basic cleavage sites for furin-like pro-protein convertases (FPPC). Most of the Class-3 semaphorins, except for Sema3E [15], utilize neuropilin 1 (Nrp1) or neuropilin 2 (Nrp2) or both as their main binding receptor [16,17,18,19]. Like other semaphorin members, all Class-3 semaphorins contain at least two conserved basic cleavage sites for furin-like pro-protein convertases (FPPC). We summarize the progress on the role of semaphorins in metabolic disorders including obesity, adipose inflammation, brown adipose tissue, immune cell metabolism, as well as diabetic complications
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