Regulation of Blood Pressure and Phosphorylation of β1-integrin in Renal Tissue in a Rat Model of Diabetic Nephropathy.

OBJECTIVE Induction of hypertension by diabetic nephropathy (DN) may be dependent on increased renin secretion from juxtaglomerular cells (JGC). To reveal that the mechanisms of cell adhesion and cell motility associated with β1-integrin phosphorylation contribute to pressure sensing in JGC, we tested the β1-integrin phosphorylation levels in renal tissue and the relationship between β1-integrin phosphorylation and the expression of renin. METHODS The DN rat model was generated by intravenous injection of streptozotocin (STZ, 60 mg/kg body weight). Immunohistochemistry and an imaging analysis were performed to detect and evaluate the β1-integrin phosphorylation levels in renal tissue. Quantitative real-time polymerase chain reaction was also performed to evaluate renin mRNA levels. RESULTS We found that the serine-785 and threonine-788/789 sites of β1-integrin are specifically phosphorylated in macula densa and JGC, respectively, and that changes in their expression during the progression of DN are associated with the production of renin. Phosphorylation of these β1-integrins increased or decreased with changes of the renin expression during the progression of DN. In particular, phosphorylation of threonine-788/789 was negatively correlated with the expression of renin. CONCLUSION These findings suggest that the phosphorylation of β1-integrin may contribute to the regulatory mechanism of renin production in JGC.