Diabetic nephropathy (DN) and hypertension mutually exacerbate each other, but many aspects of the mechanisms of these two pathologies remain unclear. The juxtaglomerular cells (JGC) secrete renin and trigger the renin-angiotensin-aldosterone system involved in blood pressure regulation. Integrins (Itgs) are cell surface proteins that interact with the extracellular matrix and transduce intracellular signals in response to extracellular stimuli. There are several phosphorylation sites in the β chain, and phosphorylation plays an important role in the cell-binding ability and intracellular signaling functions of Itgs. Our previous immunohistochemical analysis of renal tissue sections of diabetic patients showed that β1 Itg, a cellular matrix adhesion factor, undergoes JGC-specific phosphorylation. To characterize the relationship between the phosphorylated β1 (pβ1) Itg and renin expression in DN, the following studies were conducted in rats with streptozotocin (STZ)-induced diabetes.
Immunohistochemical analysis of the prepared sections showed JGC-specific phosphorylation of β1 Itg in the kidneys of diabetic rats. Immunofluorescent staining of these kidney tissue specimens confirmed the coexpression of pβ1 Itg and renin in JGC.
The mRNA levels of pβ1 Itg decreased continuously with time in diabetic rats after the onset of diabetes, till month 2. However, the mRNA levels of pβ1 Itg increased subsequently, but ultimately showed recovery to the baseline level. In contrast, the renin mRNA ratio exhibited an inverse correlation with pβ1 Itg. Quantification by image analysis of confocal laser microscopic images confirmed the negative correlation between pβ1 Itg and renin.
Our results showed a negative correlation between pβ1 Itg and renin expression in renal JGC, suggesting a link between β1 Itg and the regulatory system that controls renin production and secretion.
M. Toyoda: None. N. Saito: None. M. Kimura: None. H. Moriya: None. K. Sawada: None. M. Fukagawa: None.