Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Nat Rev Nephrol. 2018 Apr;14(4):231-245. doi: 10.1038/nrneph.2017.186. Epub 2018 Jan 30.
An accumulating body of evidence suggests that renin-expressing cells have developed throughout evolution as a mechanism to preserve blood pressure and fluid volume homeostasis as well as to counteract a number of homeostatic and immunological threats. In the developing embryo, renin precursor cells emerge in multiple tissues, where they differentiate into a variety of cell types. The function of those precursors and their progeny is beginning to be unravelled. In the developing kidney, renin-expressing cells control the morphogenesis and branching of the renal arterial tree. The cells do not seem to fully differentiate but instead retain a degree of developmental plasticity or molecular memory, which enables them to regenerate injured glomeruli or to alter their phenotype to control blood pressure and fluid-electrolyte homeostasis. In haematopoietic tissues, renin-expressing cells might regulate bone marrow differentiation and participate in a circulating leukocyte renin-angiotensin system, which acts as a defence mechanism against infections or tissue injury. Furthermore, renin-expressing cells have an intricate lineage and functional relationship with erythropoietin-producing cells and are therefore central to two endocrine systems - the renin-angiotensin and erythropoietin systems - that sustain life by controlling fluid volume and composition, perfusion pressure and oxygen delivery to tissues. However, loss of the homeostatic control of these systems following dysregulation of renin-expressing cells can be detrimental, with serious pathological events.
越来越多的证据表明,肾素表达细胞在进化过程中作为一种维持血压和体液平衡以及对抗多种内稳态和免疫威胁的机制而发展起来。在胚胎发育过程中,肾素前体细胞出现在多种组织中,并分化为多种细胞类型。这些前体细胞及其后代的功能开始被揭示。在发育中的肾脏中,表达肾素的细胞控制着肾动脉树的形态发生和分支。这些细胞似乎没有完全分化,而是保留了一定程度的发育可塑性或分子记忆,使它们能够再生受损的肾小球,或改变其表型以控制血压和体液电解质平衡。在造血组织中,表达肾素的细胞可能调节骨髓分化,并参与循环白细胞肾素-血管紧张素系统,该系统作为对抗感染或组织损伤的防御机制。此外,表达肾素的细胞与促红细胞生成素产生细胞有着复杂的谱系和功能关系,因此是维持生命的两个内分泌系统——肾素-血管紧张素系统和促红细胞生成素系统的核心,通过控制体液量和成分、灌注压和向组织输送氧气来维持生命。然而,这些系统的内稳态控制失调后,肾素表达细胞的失调可能会导致严重的病理事件,从而对其产生不利影响。