Biomedical subjects
Publications and source records attributed to B Baggio.
A phospholipase A2 activating a phospholipid renin preinhibitor into a lysophospholipid renin inhibitor has been isolated from rat kideny and partially characterized.
In order to verify the possibility than human plasma and kidney can activate a renin preinhibitor (Phospholipid) into inhibitor (lysophospholipid), constant quantities of preinhibitor were added to plasma and kidney homogenate. Addition of preinhibitor to plasma did not modify the quantity of Angiotensin I that developed. On the other hand, addition of preinhibitor to crude kidney homogenate, followed by incubation with human angiotensinogen, caused a significant fall in the quantity of Angiotensin I generated. While plasma is deficient in the specific enzyme delegated to the transformation of preinhibitor into inhibitor, it appears that this enzyme is present in the kidney.
Compensatory renal hypertrophy has been induced in rats by uninephrectomy. Tissue kallicrein concentration of the remaining kidney was evaluated 5, 10, 15 and 20 days after operation. The previously removed kidneys were used as controls. In the hypertrophic kidney the kallicrein increases progressively up to 20 days after uninephrectomy. Since kallicrein generates kinins, potent vasodilators, it is suggested that the increase in renal blood flow observed after uninephrectomy might be promoted by an overproduction of kinins.
1. The kallikrein content of kidneys from spontaneously hypertensive and normal rats at birth and at age 37 days was determined. 2. Kallikrein values were significantly lower in the hypertensive rats. 3. It is suggested that the lowered kallikrein may be related to the development of hypertension.
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Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of diabetic retinopathy but its role in diabetic nephropathy is only speculative so far. It has been shown that in renal cortex of normal kidneys, glomerular and tubular epithelial cells express VEGF and that VEGF 165 is the predominant isoform. Two VEGF receptors, KDR (kinase domain region) and Flt-1 (fms-like tyrosine kinase) are co-expressed by glomerular and peritubular capillary endothelial cells. However, VEGF and VEGF receptors are predominantly expressed at glomerular level. We recently demonstrated that in type 2 diabetic patients glomerular qualitative and quantitative changes of VEGF mRNA expression are associated with functional and structural renal changes. In the present work we focused on the tubulo-interstitial compartment; by reverse transcription/polymerase chain reaction (RT/PCR) we evaluated the expression of VEGF, KDR, Flt-1 and the relationship between the two main type of VEGF isoforms, VEGF121 and VEGF165 in the tubulo-interstitium of type 2 diabetic patients. Patients were divided in three category on the basis of renal structure pattern: CI, with normal or near normal renal structure; CII, with glomerular and tubulo-interstitial lesions occurring in parallel (typical diabetic nephropathology); CIII, with atypical pattern of renal injury, i.e., more severe tubulo-interstitial and vascular than glomerular changes. Comparison between the two cortical compartments revealed that, both in glomeruli and in tubulo-interstitium. VEGF121 isoform exceed VEGF165 while Flt-1 was significantly lower in glomeruli. CIII patients had the lowest tubulo-interstitial level of VEGF and Flt-1 mRNAs. These results suggest that the transcriptional shifting from VEGF165 to VEGF121 isoform and the unbalanced FIt-1 expression between tubulo-interstitium and glomeruli could be involved in the pathogenesis of diabetic nephropathy. Furthermore, at least in CIII patients, down-regulation of the VEGF-Flt-1 system could be involved in the mechanisms leading to tubulointerstitial diabetic lesions.
Molecular biology techniques, to be applicable to a diagnostic renal biopsy specimen, should (1) be highly sensitive to be performed on a very small quantity of tissue; (2) be quantitative because they have to analyze genes normally expressed in the tissue and (3) allow the analysis of as large a number of genes as possible. Among different methods, only the reverse-transcriptase polymerase chain reaction (RT/-PCR) might comply with previous requisites, but the few RT/-PCR examples on renal biopsies in the literature do not allow starting RNA quantification and quality control; furthermore they have the drawback of analyzing only few genes. In an ongoing study to assess the expression of a number of genes in glomeruli and in tubulointerstitium of patients with different nephropathies, we developed a comparative RT/-PCR kinetic strategy based on the purification and quantification of total glomerular and tubulointerstitial RNA and on the use of an internal standard, the housekeeping gene G3PDH. We demonstrate that in microdissected diagnostic renal biopsies (1) glomerular and interstitial starting RNA can be quantified; (2) the G3PDH gene may be used both as an internal standard and as an indirect marker of RNA integrity; (3) as low as 28 ng of total RNA is sufficient to obtain PCR products of eight genes, and (4) it is worth to operate on microdissected biopsy specimens because of the different expression of genes in the two renal compartments.