Cystic kidneys associated with connective tissue disorders

Kaplan, Bernard S.; Kaplan, Paige; Kessler, Ada

doi:10.1002/(sici)1096-8628(19970317)69:2<133::aid-ajmg4>3.0.co;2-q

Cited by 19 publications

(12 citation statements)

References 35 publications

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“…For example, a hypomorphic mutation of laminin ␣5, a major tubular basement membrane component, results in aberrant accumulation of laminin and cystic renal disease in mice (13). Various connective tissue dysplasias have also been associated with cystic kidneys in humans (14).…”

Section: Discussionmentioning

confidence: 99%

Increased Occurrence of Pericardial Effusion in Patients with Autosomal Dominant Polycystic Kidney Disease

Qian

Hartman

King

et al. 2007

Clinical Journal of the American Society of Nephrology

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Background and objectives: Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disease with prominent connective tissue manifestations. A frequent occurrence of asymptomatic pericardial effusion has been observed in patients with ADPKD.Design, setting, participants, & measurements: Consecutive computed tomography scans from 60 patients with ADPKD (group 1), 100 patients without ADPKD and with serum creatinine concentration of >1.1 mg/dl (group 2), and 100 potential kidney donors (group 3) were retrospectively examined. Pericardial effusion was graded from 0 to 4 on the basis of the distance between the parietal and visceral pericardia at mid, mid-low, and low levels of the heart on transaxial computed tomography scan sections.Results: Twenty-one (35%) of 60 patients in group 1 were found to have pericardial effusion, compared with 9 (9%) and 4 (4%) patients in groups 2 and 3, respectively. Ten of the 21 patients with pericardial effusion in group 1 but none of the patients in groups 2 and 3 had moderate to high effusion scores. The presence and severity of pericardial effusion were not associated with age, renal dysfunction, or hypertension. All pericardial effusions were asymptomatic.Conclusions: Pericardial effusion occurs with an increased frequency in patients with ADPKD, possibly as a result of increased compliance of the parietal pericardium. Although frequently moderate to large, these effusions are generally well tolerated and clinically inconsequential.

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Section: Discussionmentioning

confidence: 99%

Increased Occurrence of Pericardial Effusion in Patients with Autosomal Dominant Polycystic Kidney Disease

Qian

Hartman

King

et al. 2007

Clinical Journal of the American Society of Nephrology

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“…38,39 Moreover, aneurysms and enhanced tissue fragility do also occur in Ehlers-Danlos syndrome that to some extent is mimicked by the phenotype of Bgn-/0 mice. 40,41 In both syndromes the occurrence of renal cysts has been reported, 42,43 which might be because of additional abnormalities in connective tissue based on the coincidence of other gene mutations. In addition, altered expression of decorin and biglycan has been described in patients with Marfan syndrome, suggesting a molecular relationship between these proteoglycans and fibrillin-1.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Fibrillin-1 by Biglycan and Decorin Is Important for Tissue Preservation in the Kidney During Pressure-Induced Injury

Schaefer

Mihálik

Bábelová

et al. 2004

The American Journal of Pathology

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There is growing evidence that the two small leucinerich proteoglycans biglycan and decorin regulate the assembly of connective tissues and alter cell behavior during development and pathological processes. In this study, we have used an experimental animal model of unilateral ureteral ligation and mice deficient in either biglycan or decorin. We discovered that pressure-induced injury to the wild-type kidneys led to overexpression of decorin, biglycan, fibrillin-1, and fibrillin-2. In contrast, in biglycan-deficient kidneys the overexpression of fibrillin-1 was markedly attenuated and this was associated with cystic dilatation of Bowman's capsule and proximal tubules. Notably, we found that in ligated kidneys from decorin-null mice, fibrillin-1 expression was initially enhanced to the same extent as in wild-type animals. However, long-term obstruction resulted in down-regulation of fibrillin-1 and concurrent cystic dilatation of Bowman's capsule in 33% of kidneys at 5 months after obstruction. In all of the genotypes, no differences in fibrillin-2 expression were observed. These in vivo data correlated with a significant induction of fibrillin-1 expression in renal fibroblasts and mesangial cells by recombinant biglycan and decorin. Biglycan and decorin belong to the family of small leucine-rich proteoglycans (SLRPs), which are characterized by core proteins with centrally located leucine-rich motifs flanked by cysteine clusters and by one (decorin) or two (biglycan) chondroitin/dermatan-sulfate side chains. SLRPs are primarily considered to play a role in collagen fibril formation and stability.

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“…for understanding the fibrotic defects that are often associated with PKD (Cuppage et al, 1980;Wilson et al, 1992), as well as understanding other Pkd1 matrix-associated phenotypes, including intracranial aneurysm (Brooke et al, 2003;Ruigrok et al, 2005); vascular fragility and maintenance of the aortic wall ECM (Kim et al, 2000;Hassane et al, 2007); overlapping connective tissue disorders (Somlo et al, 1993;Kaplan et al, 1997); abdominal wall hernia (Morris-Stiff et al, 1997); and increased pericardial compliance associated with pericardial effusion in ADPKD patients (Qian et al, 2007). Our finding that a reduction in matrix gene expression by col2a1 knockdown can rescue polycystin axis curvature defects suggests that abnormalities in matrix composition or integrity are likely to be developmental defects linked directly to polycystin function, as opposed to secondary consequences of tissue damage or deformity.…”

Section: Research Articlementioning

confidence: 99%

The ADPKD genespkd1a/bandpkd2regulate extracellular matrix formation

Mangos

Lam

Zhao

et al. 2010

Disease Models &Amp; Mechanisms

136

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SUMMARYMutations in polycystin1 (PKD1) account for the majority of autosomal dominant polycystic kidney disease (ADPKD). PKD1 mutations are also associated with vascular aneurysm and abdominal wall hernia, suggesting a role for polycystin1 in extracellular matrix (ECM) integrity. In zebrafish, combined knockdown of the PKD1 paralogs pkd1a and pkd1b resulted in dorsal axis curvature, hydrocephalus, cartilage and craniofacial defects, and pronephric cyst formation at low frequency (10-15%). Dorsal axis curvature was identical to the axis defects observed in pkd2 knockdown embryos. Combined pkd1a/b, pkd2 knockdown demonstrated that these genes interact in axial morphogenesis. Dorsal axis curvature was linked to notochord collagen overexpression and could be reversed by knockdown of col2a1 mRNA or chemical inhibition of collagen crosslinking. pkd1a/b-and pkd2-deficient embryos exhibited ectopic, persistent expression of multiple collagen mRNAs, suggesting a loss of negative feedback signaling that normally limits collagen gene expression. Knockdown of pkd1a/b also dramatically sensitized embryos to low doses of collagen-crosslinking inhibitors, implicating polycystins directly in the modulation of collagen expression or assembly. Embryos treated with wortmannin or LY-29400 also exhibited dysregulation of col2a1 expression, implicating phosphoinositide 3-kinase (PI3K) in the negative feedback signaling pathway controlling matrix gene expression. Our results suggest that pkd1a/b and pkd2 interact to regulate ECM secretion or assembly, and that altered matrix integrity may be a primary defect underlying ADPKD tissue pathologies.

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Cystic kidneys associated with connective tissue disorders

Cited by 19 publications

References 35 publications

Increased Occurrence of Pericardial Effusion in Patients with Autosomal Dominant Polycystic Kidney Disease

Increased Occurrence of Pericardial Effusion in Patients with Autosomal Dominant Polycystic Kidney Disease

Regulation of Fibrillin-1 by Biglycan and Decorin Is Important for Tissue Preservation in the Kidney During Pressure-Induced Injury

The ADPKD genespkd1a/bandpkd2regulate extracellular matrix formation

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