Puberty permits increased expression of renal transforming growth factor-?1 in experimental diabetes

Lane, Pascale H.; Snelling, Dustin M.; Hollman, Alecia; Langer, William J.

doi:10.1007/s004670100020

Cited by 14 publications

(17 citation statements)

References 54 publications

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“…By acting via an autocrine or paracrine mechanism, this growth factor contributes to diabetic renal and glomerular hypertrophy (31). Our lab previously showed that sexually mature male DM rats had increased expression and activity of TGF-␤ 1 , along with increased glomerular hypertrophy, compared with prepubertal male DM rats (17). We have also demonstrated sexrelated differences in the renal TGF-␤ 1 system in normal rats (16).…”

mentioning

confidence: 91%

Estrogen receptor α-mediated events promote sex-specific diabetic glomerular hypertrophy

Lovegrove¹,

Sun²,

Gould³

et al. 2004

American Journal of Physiology-Renal Physiology

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differences in the incidence and progression of renal diseases suggest a protective role for estrogen. This study examined the role of estrogen receptor ␣ (ER␣)-mediated events in normal and diabetic renal and glomerular growth. Wild-type and ER␣-null mice (ERKO) were observed over 2 wk of streptozocin-induced diabetes. Blood glucose was monitored, and insulin was given daily to maintain levels of 250 -350 mg/dl. Body weight, kidney weight, glucose, insulin, renal transforming growth factor-␤1, and glomerular area were examined for effects of sex, genotype, and diabetes. Genotype had no effect on glomerular or renal size in male mice regardless of metabolic state. Nondiabetic female ERKO mice had kidney weights approaching those of wild-type males and much greater than those of wild-type females (0.15 Ϯ 0.04 vs. 0.11 Ϯ 0.04 g; P Ͻ 0.001). When only diabetic mice were studied, sex and/or genotype showed no effect on renal weight. Diabetic female ERKO mice had smaller glomerular areas than wild types (2,799 Ϯ 159 vs. 3,409 Ϯ 187 m 2 ; P ϭ 0.01). Glomerular areas were similar in diabetic wild-type and ERKO males (3,020 Ϯ 199 vs. 3,406 Ϯ 176 m 2 ). Transforming growth factor-␤1 levels, expressed as picograms per milligram total protein, were similar in diabetic wild-type and ERKO males (1.0 Ϯ 0.6 vs. 0.9 Ϯ 0.6). In diabetic females, wild types had significantly higher levels of this growth factor than ERKO mice (3.8 Ϯ 0.7 vs.

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mentioning

confidence: 91%

Estrogen receptor α-mediated events promote sex-specific diabetic glomerular hypertrophy

Lovegrove¹,

Sun²,

Gould³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…The onset of microalbuminuria, the earliest clinical manifestation of diabetic kidney disease, is so rare before puberty that screening is usually not recommended prior to the onset of sexual development [2,3]. Animal models also show differences in early renal and glomerular growth responses to the diabetic state [4][5][6][7][8][9]. Functional differences in diabetic kidney disease cannot be shown in rodent models, probably because of the short duration of prepubertal disease relative to the disease period required for renal dysfunction to develop.…”

Section: Introductionmentioning

confidence: 99%

Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor

et al. 2007

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Puberty unmasks or accelerates the nephropathy of diabetes mellitus (DM). We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-beta) signaling system would be differentially regulated in male rats depending on their age at onset of DM. Littermates were started on the 6-week protocol at 4 weeks or 14 weeks of age. Renal cortical RNA was isolated and analyzed using gene chips with more than 30,000 transcripts. Age-specific effects of DM were demonstrated for 1,760 transcripts. Analysis then focused on 89 genes involved in the TGF-beta signaling pathway. Three of these genes showed age-dependent responses to DM, confirmed by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Connective tissue growth factor (CTGF) mRNA and protein were both increased approximately 30% in the renal cortex 6 weeks after adult-onset DM, with no alteration in either parameter after juvenile onset. Follistatin and avian myelocytomatosis viral oncogene homolog mRNA both showed a similar age-related pattern of response to DM, but protein levels did not parallel mRNA for either of these gene products. Given the known roles of CTGF in progressive nephropathies, it is an attractive candidate to explain pubertal acceleration or unmasking of the kidney disease of diabetes.

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“…In addition, the impact on kidney function of physiologic changes associated with pubertal growth and development in this population is unknown. These changes may accelerate the progression of calcineurin inhibitor induced nephrotoxicity as has been noted in other chronic nephropathies (15)(16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Glomerular Filtration Rate Following Pediatric Liver Transplantation—The SPLIT Experience

Campbell

Martin

et al. 2010

American Journal of Transplantation

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Impaired kidney function is a well-recognized complication following liver transplantation (LT). Studies of this complication in children have been limited by small numbers and insensitive outcome measures.Our aim was to define the prevalence of, and identify risk factors for, post-LT kidney dysfunction in a multicenter pediatric cohort using measured glomerular filtration rate (mGFR). We conducted a crosssectional study of 397 patients enrolled in the Studies in Pediatric Liver Transplantation (SPLIT) registry, using mGFR < 90 mL/min/1.73 m 2 as the primary outcome measure. Median age at LT was 2.2 years. Primary diagnoses were biliary atresia (44.6%), fulminant liver failure (9.8%), metabolic liver disease (16.4%), chronic cholestatic liver disease (13.1%), cryptogenic cirrhosis (4.3%) and other (11.8%). At a mean of 5.2 years post-LT, 17.6% of patients had a mGFR < 90 mL/min/1.73 m 2 . In univariate analysis, factors associated with this outcome were transplant center, age at LT, primary diagnosis, calculated GFR (cGFR) at LT and 12 months post-LT, primary immunosuppression, early post-LT kidney complications, age at mGFR, height and weight Z-scores at 12 months post-LT. In multivariate analysis, independent variables associated with a mGFR <90 mL/min/1.73 m 2 were primary immunosuppression, age at LT, cGFR at LT and height Z-score at 12 months post-LT.

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Puberty permits increased expression of renal transforming growth factor-?1 in experimental diabetes

Cited by 14 publications

References 54 publications

Estrogen receptor α-mediated events promote sex-specific diabetic glomerular hypertrophy

Estrogen receptor α-mediated events promote sex-specific diabetic glomerular hypertrophy

Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor

Glomerular Filtration Rate Following Pediatric Liver Transplantation—The SPLIT Experience

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