Glomerular Expression of α2(IV) and α5(IV) Chains of Type IV Collagen in Patients with IgA Nephropathy

Kamimura, Hirokazu; Honda, Kazuho; Nitta, Kosaku; Horita, Shigeru; Kobayashi, Hideo; Uchida, Keiko; Yamaguchi, Yutaka; Yumura, Wako; Nihei, Hiroshi

doi:10.1159/000057603

Cited by 14 publications

(14 citation statements)

References 14 publications

(19 reference statements)

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“…Although the exact molecular mechanisms of renal fibroproliferative diseases are not yet clear, increased synthesis and deposition of types I, III IV, and VI collagens have been detected in chronic progressive fibrotic renal diseases including IgA nephropathy, diabetic nephropathy ( fig. 2) and hypertensive nephrosclerosis [28][29][30]. Morphological changes in various stages of renal diseases range from activation and proliferation of intrarenal cells to severe glomerulosclerosis and tubulointerstitial fibrosis.…”

Section: Renal Fibroproliferative Diseasesmentioning

confidence: 99%

Heat Shock Protein 47 and Renal Fibrogenesis

Taguchi

2005

Contributions to Nephrology

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Recent research has greatly increased our knowledge regarding the molecular mechanisms of collagen synthesis and processing. Heat specific shock protein (HSP47) is a collagen-specific molecular chaperone, and helps in post-translational modifications of procollagens, during biosynthesis of collagen. Both in vivo and in vitro studies have convincingly demonstrated that HSP47 is localized in the endoplasmic reticulum of collagen-producing cells, and that its synthesis is closely associated with the rate of procollagen assembly. Recent studies are directed towards the pathological relevance of HSP47 in tissue scarring, a process that is characterized by excessive accumulation of collagens. It appears likely that increased levels of HSP47 in fibrotic diseases assist in increased assembly of procollagen, and thereby help in excessive accumulation of collagens in the fibrotic mass. Such profibrotic effects of HSP47 suggest that modulation of HSP47 expression in scarring diseases might alter the course of fibrotic diseases. In this brief article, we review the role of HSP47 in renal fibrotic diseases and its relevance to other scarring diseases.

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Section: Renal Fibroproliferative Diseasesmentioning

confidence: 99%

Heat Shock Protein 47 and Renal Fibrogenesis

Taguchi

2005

Contributions to Nephrology

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“…IgA nephropathy patients without hematuria may have nephrosclerosis or hereditary nephritis with concomitant glomerular IgA deposition, because 4 % of normal persons without urinary abnormalities are reported to have glomerular IgA deposition on postmortem examination after accidental death [7]. Concomitant glomerular IgA deposition has been reported in hereditary nephritis, including thin basement membrane disease [8–10], mild Alport syndrome [11], focal segmental glomerulosclerosis [12], and complement factor abnormalities [13]. Moreover, the CR rate in patients without proteinuria (mainly hematuria alone) is relatively low, 60.8 % compared to approximately 73.0 % in patients with 0.3–0.69 g/day of urinary protein.…”

Section: Discussionmentioning

confidence: 99%

Estimated glomerular filtration rate and daily amount of urinary protein predict the clinical remission rate of tonsillectomy plus steroid pulse therapy for IgA nephropathy

2013

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BackgroundThis retrospective study was designed to estimate the clinical remission (CR) rate of tonsillectomy plus steroid pulse (TSP) therapy in patients with IgA nephropathy.MethodsBased on 292 of 302 patients with IgA nephropathy treated at 11 Japanese hospitals, we constructed heat maps of the CR rate at 1 year after TSP with the estimated glomerular filtration rate (eGFR), grade of hematuria, pathological grade, number of years from diagnosis until TSP, and age at diagnosis on the vertical axis and the daily amount of urinary protein (urinary protein) on the horizontal axis. We compared subgroups usinge Student’s t test, the chi-square test with Yates correction, or Fisher’s exact probability test.ResultsThe first heat map of eGFR and urinary protein showed that the CR rate was 71 % (CR vs. non-CR, 96 vs. 40) in patients with eGFR greater than 30 ml/min/1.73 m2 and 0.3–1.09 g/day of urinary protein. However, the CR rate in patients with more than 1.50 g/day of urinary protein was approximately 30 %. The second heat map of grade of hematuria and urinary protein revealed that the CR rate is 72 % (CR vs. non-CR, 93 vs. 37) in patients with more than 1+ hematuria and 0.3–1.09 g/day of urinary protein; however, it was 28.6 % in patients with no hematuria. The third heat map of pathological grade and urinary protein demonstrated that the highest CR rate was 83 % (CR vs. non-CR, 52 vs. 11) in patients with pathological grade I or II disease and less than 1.09 g/day of urinary protein, as opposed to 22 % (CR vs. non-CR, 9 vs. 32) in patients with pathological grade III or IV disease and more than 2.0 g/day of urinary protein. The fourth heat map of the number of years from diagnosis until TSP and urinary protein revealed that the former did not influence the CR rate in patients with less than 1.09 g/day of urinary protein. However, in patients with more than 1.10 g/day of urinary protein, the CR rate of the subgroup with less than 6 years was 43 % (CR vs. non-CR; 23 vs. 54) compared to 23 % (CR vs. non-CR, 11 vs. 48; P = 0.01) in the subgroup with more than 6 years. The fifth heat map of age at diagnosis and urinary protein showed that the CR rate is approximately 72 % (CR vs. non-CR, 73 vs. 28) in patients older than 19 years at diagnosis with 0.3–1.09 g/day of urinary protein.ConclusionsThe daily amount of urinary protein is an important predictor of the CR rate after TSP in IgA nephropathy patients. Heat maps are useful tools for predicting the CR rate associated with TSP.

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“…Analyzing the degree of protein expression, Kim et al [8] noticed an overproduction of col(IV)α5 protein in kidney tissue of 13 patients with diabetic nephropathy, and 21 patients with membranous nephropathy. By contrast, other authors reported a reduction of col(IV)α5, and an increased glomerular expression of col(IV)α2, in patients with IgA nephropathy [9, 10]. …”

Section: Introductionmentioning

confidence: 87%

Alterations of Type IV Collagen α Chains in Patients with Chronic Acquired Glomerulopathies: mRNA Levels, Protein Expression and Urinary Loss

et al. 2007

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Background: Type IV collagen is a major structural component of the normal kidney glomerulus. However, its role in chronic acquired glomerulopathies has been only partially elucidated. Methods: Urinary levels of col(IV)α1, col(IV)α3 and col(IV)α5 collagen chains were analyzed in 107 patients with chronic acquired glomerulopathies. In a subgroup of 33 patients, tissue mRNA levels, protein expression and urinary excretion were evaluated for all col(IV)α chains, from col(IV)α1 to col(IV)α5. The renal specimens were examined to get a semiquantitative score of the acute and chronic activity of the histological lesions. Urines obtained from 13 healthy subjects and 10 normal renal tissue samples were used as controls. Results: Urinary levels of col(IV)α1, col(IV)α3, col(IV)α5 chains were significantly higher in patients than in controls [p < 0.01 for all], while only col(IV)α1 and col(IV)α3 urinary excretion correlated with the degree of chronic histological damage [col(IV)α1 R = 0.44, p < 0.001; col(IV)α3: R = 0.47, p < 0.001]. Compared with controls, patients showed a renal expression of mRNA for col(IV)α5 chain significantly higher [p = 0.001], while having a significantly lower protein expression of col(IV)α3, col(IV)α4 and col(IV)α5 chains [p < 0.01 for all]. Conclusion: Patients with chronic acquired glomerulopathies show important alterations in the col(IV)α chain network mimicking some molecular features of the X-linked Alport’s syndrome. Further studies are needed to show whether urinary levels of the col(IV)α chains may be used as markers for monitoring renal injury.

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Glomerular Expression of α2(IV) and α5(IV) Chains of Type IV Collagen in Patients with IgA Nephropathy

Cited by 14 publications

References 14 publications

Heat Shock Protein 47 and Renal Fibrogenesis

Heat Shock Protein 47 and Renal Fibrogenesis

Estimated glomerular filtration rate and daily amount of urinary protein predict the clinical remission rate of tonsillectomy plus steroid pulse therapy for IgA nephropathy

Alterations of Type IV Collagen α Chains in Patients with Chronic Acquired Glomerulopathies: mRNA Levels, Protein Expression and Urinary Loss

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