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Repair of injured tissues requires angiogenesis, the growth of new blood vessels from pre-existing ones. Cutaneous wound healing is a complex and dynamic process by which skin tissue repairs itself after injury; however, how endothelial cells and pericytes form new blood vessels during cutaneous wound angiogenesis remains unclear. We recently developed a fluorescence-based live imaging system to analyze cutaneous wound angiogenesis in adult zebrafish. Employing this system, we found that endothelial cells and pericytes remain in a quiescent state in normal skin tissue, whereas cutaneous injury immediately activates both types of cells to induce angiogenesis. At 2 days post-injury (dpi), the injured vessels elongated, and some uninjured vessels became tortuous and began to sprout new branches. Then, vessel sprouting, elongation, bifurcation, and anastomosis progressively occurred to form the tortuous and disorganized vascular networks observed at 6 dpi. Thereafter, blood vessel tortuosity gradually decreased through the regression of excessive vessels, thereby leading to the formation of well-organized vessel networks at 42 dpi. Pericytes are thought to detach from the vessel wall to promote endothelial cell sprouting upon the induction of angiogenesis. However, not only endothelial cells but also pericytes proliferated to form pericyte-covered tortuous blood vessels in response to cutaneous injury, revealing an unexpected role of pericytes in cutaneous wound angiogenesis. Therefore, this live-imaging system for adult zebrafish is anticipated to make a valuable contribution to research advancements in understanding the angiogenesis that occurs during tissue repair.

Pericytes are mural cells embedded in the basal membrane surrounding endothelial cells in capillary and small vessels (from precapillary arterioles to postcapillary venules). They exist with a high coverage ratio to endothelial cells in the brain and play crucial roles in the formation and maintenance of the blood-brain barrier and the control of blood flow through a close interaction with endothelial cells. Thus, intactness of pericyte is absolutely needed for neuronal/brain functions. Ageing, life-style diseases, hypoperfusion/ischemia, drugs, and genetic factors can primarily cause pericyte dysfunctions, thereby leading to the development or progression of various brain disorders, including cerebrovascular diseases. Because pericytes also play an important role in tissue repair after brain injuries, they have received much attention as a therapeutic target even from the standpoint of functional recovery.

In chronic kidney disease (CKD), progressive nephron loss causes tubulointerstitial fibrosis and progressive tubular injury. Recent identification of the major cell populations of myofibroblast precursors in the kidney has enabled us to dissect the fibrogenic process after tubular injury. Kidney pericytes are a possible precursor of myofibroblasts, and may be promising targets for treating fibrogenesis. Our recent studies have shown that pericytes activate Toll-like receptor (TLR) 2/4- and myeloid differentiation primary response 88 (MyD88)-dependent proinflammatory signaling in response to renal tubular injury. We also found active roles of inflammasomes in kidney pericytes, leading to interleukin (IL)-1β and IL-18 secretion. Genetic ablation of MyD88 in pericytes, or pharmacological inhibition of MyD88 signaling by an IL-1 receptor-associated kinase 4 (IRAK4) inhibitor, halted interstitial fibrosis after renal tubular injury. Our data indicate that pericytes not only contribute to interstitial fibrosis by aberrant wound-healing responses, but also serve as innate immune surveillance cells that regulate the inflammatory process, exacerbating tubular injury by the release of cytokines and chemokines. On the other hand, our recent study using a microarray analysis aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage in patients with CKD. The results indicated that 5 genes were up-regulated in the kidney of CKD patients, and that their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury. These findings provide important information for the development of diagnostic tools and therapeutic agents for predicting and preventing progressive renal disease.