Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 413

8.5.3.6 Renin Phenotype

Renin is involved in the regulation and maintenance of blood pressure and
fluid-electrolyte balance. During embryogenesis, before the development and
maturation of the kidney vasculature, the undifferentiated metanephric blastema
contains

cells are
distributed throughout the intrarenal arterial tree, inside glomeruli and in
the interstitium. As maturation continues, renin production is restricted to
myoepithelioid, granulated juxtaglomerular cells in walls of afferent arterioles
at entrances to renal glomeruli. Non-juxtaglomerular cells of afferent arterioles
and within glomeruli that descend from renin

renin-expressing cells [ 756 ]. During fetogenesis, renin +

progenitor cells differentiate into
arteriolar smooth muscle, mesangial, and interstitial cells, as well as a subset
of tubular cells. Hence, in adults, renin is synthesized and released only by
juxtaglomerular cells of the kidney.
Renin production and secretion rely on the cAMP pathway. Renin transcription
is launched when cAMP responsive element (CRE)-binding (CREB) protein links
to CREB-binding protein (CBP) and P300 coactivators that are histone acetyltrans-
ferases, which can remodel chromatin and facilitate access of repressor or enhancer
transcription factors to gene promoters. The resulting CREB-CBP-P300 complex
connects to CRE in the renin gene promoter.
Dedifferentiation and reacquisition of the renin phenotype in arteriolar smooth
myocytes that originate from renin-expressing cells during in utero life, which
is required when the fluid-electrolyte balance is disturbed, i.e., during sustained
hypotension, dehydration, hemorrhage, and sodium depletion, enable increase
of circulating renin level. In fact, increase in the number of renin-expressing
cells results from: (1) augmentation of the number of juxtaglomerular apparatus
producing renin; (2) elevation of the number of renin

+

cells per juxtaglomerular
apparatus; and, mainly, (3) retransformation of vascular smooth myocytes of
afferent arterioles upstream from glomeruli into renin

+

cells. Both CBP and P300
enable the maintenance of identity of cells from the renin lineage, i.e., to retain
memory of renin phenotype in renin

+

+ cell descendants, and regain the expression

of the renin gene [ 756 ].

8.5.3.7 Macrophage-like Phenotype

Vascular smooth myocytes can acquire a scavenger receptor ScaRd1 , macrophage-

like phenotype 39 with phagocytic activity and endocytosis of modified LDLs in
atherosclerosis [ 747 ]. 40

+

These cells can indeed take up low-density liproteins

39 Macrophages produce various scavenger receptors, such as ScaRa1, ScaRa2, ScaRb1, ScaRb3,
ScaRd1, and ScaRe1.
40 Endocytic and phagocytic activities of vascular smooth myocytes are associated with synthesis
of ScaRd1, a scavenger receptor of the lysosomal-associated membrane protein family, S100a9,