AIM： To investigate renin expression in pericytes dur-ing normal kidney development and after deletion of angiotensinogen, the precursor for all angiotensins.METHODS： We examined the distribution of renin ex-pressin...AIM： To investigate renin expression in pericytes dur-ing normal kidney development and after deletion of angiotensinogen, the precursor for all angiotensins.METHODS： We examined the distribution of renin ex-pressing cells by immunoshistochemistry in the intersti-tial compartment of wild type （WT） and angiotensino-gen deficient （AGT -/-） mice at different developmental stages from embryonic day 18 （E18： WT, n = 4; AGT -/-, n = 5） and at day 1 （P1： WT, n = 5; AGT -/-, n = 5）, 5 （P5： WT, n = 7; AGT -/-, n = 8）, 10 （P10： WT, n = 3; AGT -/-, n = 5）, 21 （P21： WT, n = 7; AGT -/-, n =5）, 45 （P45： WT, n = 3; AGT -/-, n = 3）, and 70 （P70： WT, n = 2; AGT -/-, n = 2） of postnatal life. We quanti-fied the number of pericytes positive for renin at all the developmental stages mentioned above and compared the results of AGT -/- mice to their WT counterparts.RESULTS： In WT mice, renal interstitial pericytes syn-thesize renin in early life supporting a lineage relation-ship with renin cells in the vasculature. The number of pericytes positive for renin per area of 0.32 mm2 （density） in WT mice was maintained from fetal life till weaning age （E18 = 4.25 ± 0.63, P1 = 3.75 ± 0.48, P5 = 3.75 ± 0.48, P10 = 4 ± 0.71, P21 = 3.8 ± 0.58） and markedly decreased in adult life （P45 = 1.2 ± 0.37, P70 = 0.8 ± 0.20）. On the other hand, in AGT -/- mice the density of pericytes expressing renin was not signifi-cantly different from WT mice at E18 and P1： E18 = 5.75 ± 0.50 vs 4.25 ± 0.63 （ P = 0.106）, P1 = 9.25 ± 3.50 vs 3.75 ± 0.48 （ P = 0.175） but significantly increased from P5 till P70： P5 = 38.25 ± 5 vs 3.75 ± 0.48 （ P = 0.0004）, P10 = 173 ± 7.50 vs 4 ± 0.70 （ P = 5.24567 × 10^-7）, P21 = 83 ± 6.70 vs 3.8 ± 0.58 （P = 2.97358 × 10^-6）, P45 = 49 ± 3.50 vs 1.2 ± 0.37 （P = 8.18274 × 10^-7） and P70 = 17.8 ± 2.30 vs 0.8 ± 0.20 （ P = 3.51151 × 10^-5）. The AGT -/- mice showed a marked increase in the number of pericytes per field studied starting from P5, reaching its peak at P10, and then a gradually de-creasing until P70.CONCLUSION： Interstitial pericytes synthesize renin during development and the number of renin-express-ing pericytes increases in response to a homeostatic threat imposed early in life such as lack of angioten-sinogen.展开更多
基金Supported by National Institutes of Health Grants RO1 DK-091330(to Sequeira-Lopez MLS)and R37 HL066242 and RO1 HL096735the Center of Excellence in Pediatric Nephrology P50 DK096373(to Gomez RA)
文摘AIM： To investigate renin expression in pericytes dur-ing normal kidney development and after deletion of angiotensinogen, the precursor for all angiotensins.METHODS： We examined the distribution of renin ex-pressing cells by immunoshistochemistry in the intersti-tial compartment of wild type （WT） and angiotensino-gen deficient （AGT -/-） mice at different developmental stages from embryonic day 18 （E18： WT, n = 4; AGT -/-, n = 5） and at day 1 （P1： WT, n = 5; AGT -/-, n = 5）, 5 （P5： WT, n = 7; AGT -/-, n = 8）, 10 （P10： WT, n = 3; AGT -/-, n = 5）, 21 （P21： WT, n = 7; AGT -/-, n =5）, 45 （P45： WT, n = 3; AGT -/-, n = 3）, and 70 （P70： WT, n = 2; AGT -/-, n = 2） of postnatal life. We quanti-fied the number of pericytes positive for renin at all the developmental stages mentioned above and compared the results of AGT -/- mice to their WT counterparts.RESULTS： In WT mice, renal interstitial pericytes syn-thesize renin in early life supporting a lineage relation-ship with renin cells in the vasculature. The number of pericytes positive for renin per area of 0.32 mm2 （density） in WT mice was maintained from fetal life till weaning age （E18 = 4.25 ± 0.63, P1 = 3.75 ± 0.48, P5 = 3.75 ± 0.48, P10 = 4 ± 0.71, P21 = 3.8 ± 0.58） and markedly decreased in adult life （P45 = 1.2 ± 0.37, P70 = 0.8 ± 0.20）. On the other hand, in AGT -/- mice the density of pericytes expressing renin was not signifi-cantly different from WT mice at E18 and P1： E18 = 5.75 ± 0.50 vs 4.25 ± 0.63 （ P = 0.106）, P1 = 9.25 ± 3.50 vs 3.75 ± 0.48 （ P = 0.175） but significantly increased from P5 till P70： P5 = 38.25 ± 5 vs 3.75 ± 0.48 （ P = 0.0004）, P10 = 173 ± 7.50 vs 4 ± 0.70 （ P = 5.24567 × 10^-7）, P21 = 83 ± 6.70 vs 3.8 ± 0.58 （P = 2.97358 × 10^-6）, P45 = 49 ± 3.50 vs 1.2 ± 0.37 （P = 8.18274 × 10^-7） and P70 = 17.8 ± 2.30 vs 0.8 ± 0.20 （ P = 3.51151 × 10^-5）. The AGT -/- mice showed a marked increase in the number of pericytes per field studied starting from P5, reaching its peak at P10, and then a gradually de-creasing until P70.CONCLUSION： Interstitial pericytes synthesize renin during development and the number of renin-express-ing pericytes increases in response to a homeostatic threat imposed early in life such as lack of angioten-sinogen.
