Somatostatin expression in human renal cortex and mesangial cells.
Somatostatin modulates important physiologic functions of the kidney, including mesangial cell contraction, glomerular prostaglandin synthesis, and phosphate, water and sodium excretion. In diabetic nephropathy, somatostatin inhibits renal hypertrophy. High affinity somatostatin receptors are expressed in the kidney. Circulating somatostatin concentrations, however, are generally well below the affinity constants of known somatostatin receptors. Thus, we hypothesized that somatostatin is produced in the kidney and released locally to act in an autocrine/paracrine manner. Using reverse transcriptase and polymerase chain reaction (RT-PCR) analysis, we found that fresh human renal cortex and cultured human mesangial cells express somatostatin mRNA. Restriction enzyme and Southern blot analysis confirmed that RT-PCR cDNA products were derived from somatostatin mRNA. Radioimmunoassay of mesangial cell culture supernatants demonstrated SS-immunoreactive peptide (87 +/- 30 pg/ml compared to 19 +/- 9 pg/ml in medium not exposed to cells; P < 0.05). In contrast, renal cells did not transcribe detectable levels of vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) mRNA, nor did they synthesize measurable peptide. Our results demonstrate that renal cells produce somatostatin and suggest that kidney-derived somatostatin may regulate renal function in an autocrine/paracrine manner. Characterization of this pathway may lead to novel methods to alter the course of diabetic nephropathy and other renal diseases.
Turman
M A
MA
Department of Pediatrics, Ohio State University, Wexner Institute for Pediatric Research, Children's Hospital, Columbus 43205, USA.
O'Dorisio
M S
MS
O'Dorisio
T M
TM
Apple
C A
CA
Albers
A R
AR
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007672:Kidney Cortex / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger; D011863:Radioimmunoassay; D013004:Somatostatin / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D010455:Peptides; D012333:RNA, Messenger; D013004:Somatostatin