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Biomedical subjects

G E Striker

Publications and source records attributed to G E Striker.

At least 19 recordsLinked to original sources
PubMed1992

The contribution of increased collagen synthesis to human glomerulosclerosis: a quantitative analysis of alpha 2IV collagen mRNA expression by competitive polymerase chain reaction.

We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process.

Adult↗
PubMed1992

Receptor-specific increase in extracellular matrix production in mouse mesangial cells by advanced glycosylation end products is mediated via platelet-derived growth factor.

Renal disease is one of the most common and severe complications of diabetes mellitus. The hallmark of the disease, glomerulosclerosis, is characterized by an accumulation of extracellular matrix in the mesangial areas, leading to progressive obliteration of the vascular spaces. The role of the metabolic derangements of diabetes mellitus in the development of these lesions is incompletely understood. One of the consequences of hyperglycemia is the formation of advanced glycosylation end products (AGEs), which result from a series of rearrangements secondary to nonenzymatic reaction of glucose with proteins. Specific receptors for proteins modified by AGEs, present in several cell types, were recently described in human and rat mesangial cells. Furthermore, exposure of mesangial cells to AGEs was followed by an increase in fibronectin production. In the present study we show evidence that mouse mesangial cells exhibit an increase in collagen type IV mRNA and peptide synthesis after exposure to AGEs. Antibodies to AGE receptors prevent this increase, indicating that the response is AGE-receptor-mediated. In addition, anti-platelet-derived growth factor abrogates the AGE response, suggesting that platelet-derived growth factor acts as an intermediate factor. Transcription assay reveals that the elevated mRNA levels are due to an increase in the transcription rate, rather than to an increase in the stability of the message. Finally, the mRNAs coding for laminin and heparan sulfate proteoglycan are also increased after exposure to AGE, whereas glyceraldehyde 3-phosphate dehydrogenase mRNA levels remain constant. The increase in extracellular matrix mRNAs seen in the current study suggests that AGE formation in vivo may be one of the metabolic events leading to the development of diabetic glomerulosclerosis.

Animals↗
PubMed1992

Age-related changes in alpha 1- and alpha 2-chain type IV collagen mRNAs in adult mouse glomeruli: competitive PCR.

Studies of age-related changes in glomerular extracellular matrix (ECM) synthesis in normal mice have been hampered by the difficulty of isolating sufficient numbers of intact glomeruli and by the inability to quantify different mRNA species. The purpose of this study was to identify and quantitate the individual mRNAs coding for alpha 1- and alpha 2-chains of type IV collagen in isolated, single glomeruli of normal mice at different ages. These data on normal ECM synthesis were necessary for the understanding of glomerulosclerosis, a condition characterized by excess deposition of collagen. Pools of freshly microdissected adult mouse glomeruli were reverse transcribed in situ, and alpha 1-IV and alpha 2-IV collagen mRNAs were individually amplified by means of specific primers and the polymerase chain reaction (PCR), according to a previously published method. A competitive PCR assay, based on utilization of mutated cDNAs, allowed the reproducible, quantitative, and separate determination of the absolute amounts of both alpha 1-IV and alpha 2-IV mRNAs measured, as their respective cDNAs, in one-tenth of one glomerulus. The levels of alpha 1-IV and alpha 2-IV collagen mRNA were 208 +/- 36.0 x 10(-4) and 161.2 +/- 18.6 x 10(-4) amol/glomerulus in 5-wk-old mice. There were no significant age-related differences at 8, 12, and 24 wk. The mean levels over this period were 60.2 +/- 4.9 x 10(-4) for alpha 1-IV collagen mRNA and 63.9 +/- 5.8 x 10(-4) amol/glomerulus for alpha 2-IV collagen mRNA. Two of three 24-wk-old mice had mild glomerulosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Large glomerular size in Pima Indians: lack of change with diabetic nephropathy.

The mean glomerular volume, glomerular fraction of cortical volume, and percentage of obsolescent glomeruli were calculated in kidney specimens from autopsies on 34 Pima Indians, of whom 15 had non-insulin dependent diabetes mellitus and kidney disease of diabetes mellitus. These values were compared with those of black, white, and non-Pima native American individuals without diabetes mellitus. Glomerular volume in the Pima Indians was similar in the diabetic and nondiabetic subjects and significantly greater than in the white subjects. Black and non-Pima native American individuals had glomerular volumes intermediate between white individuals and Pima Indians. The mean glomerular volume was not affected by the number of obsolescent glomeruli in diabetic Pima Indians. The glomerular volume fraction was greater in the Pimas than in the other groups. These data showed that glomerular volume in the Pima Indians was significantly greater than that in white subjects. There was no difference between diabetic and nondiabetics Pimas, and glomerular size was not correlated with the presence or degree of glomerulosclerosis in this population.

Adolescent↗
PubMed1991

Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels.

Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.

Aging↗
PubMed1991

Glomerulosclerosis at both early and late stages is associated with increased cell turnover in mice transgenic for growth hormone.

The evolution of glomerulosclerosis consists of a progressive increase in mesangial matrix with gradual glomerular obliteration. The sclerotic process is thought to be irreversible and include a progressive loss of glomerular cells. To investigate this process, we selected mice transgenic for bovine growth hormone because they develop progressive glomerulosclerosis and renal failure. The sequence of histologic events in the growth hormone mice consists initially of an increase in the number of centrolobular glomerular cells, followed by an accumulation of extracellular matrix. This is accompanied by an increase in glomerular size which is disproportionate to the overall increment in kidney or body weight. The [3H]thymidine labeling index of the cells of the glomerular tuft was assessed before the development of recognizable sclerosis and at a time when the sclerosis was far advanced. The labeling index was more than five-fold increased over controls at the early time point. Contrary to what was expected, the labeling index remained at the same high levels in densely sclerotic glomeruli at the late time point. In conclusion, increased cell turnover is a significant component of the sclerotic process both at the onset and in the late stages of this model.

Animals↗