Immunohistochemical localization of collagen VI in diabetic glomeruli

Nerlich, Andreas G.; Schleicher, Erwin; Wiest, I.; Specks, Ulrich; Timpl, Rupert

doi:10.1038/ki.1994.216

Cited by 69 publications

(68 citation statements)

References 33 publications

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“…The phenotypes of cells forming the interstitial infiltrate in DN have not been precisely defined to date, most previous studies having concentrated on the glomerular changes taking place in the course of the disease process [3][4][5][6]10]. In this paper we have demonstrated a tenfold increase in the number of MC within the interstitium in DN compared with normal kidney tissue.…”

Section: Discussionsupporting

confidence: 53%

“…In diabetes there is an increased production and a reduced degradation of extracellular matrix constituents leading to their overall accumulation [2]. Many studies of DN have aimed at defining intraglomerular changes [3][4][5][6], but the mechanisms of tubulointerstitial matrix abnormalities have been infrequently considered [2]. Although several studies have attempted to define the nature of the components of extracellular matrix which accumulates in a variety of experimental and human nephropathies [1,[7][8][9][10], knowledge in this area is still rudimentary.…”

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confidence: 99%

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Mast cells and type VIII collagen in human diabetic nephropathy

Rüger¹,

Hasan²,

Greenhill³

et al. 1996

Diabetologia

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SummaryRenal injury in diabetes mellitus is associated with progressive interstitial fibrosis and extracellular matrix accumulation. However, the phenotypes of cells forming the interstitial infiltrate in diabetic nephropathy have not been precisely defined. There is increasing evidence for the association of mast cells with angiogenesis, chronic inflammatory conditions and fibrosis. We have recently shown that human mast cells can produce the non-fibrillar short chain type VIII collagen in vivo. Using immunohistochemistry, in situ hybridisation and reverse transcriptasepolymerase chain reaction, we examined the contribution of mast cells and type VIII collagen to the fibrotic changes occurring in biopsy-proven diabetic nephropathy. We observed that the number of interstitial mast cells was significantly increased in diabetic nephropathy compared with normal kidney tissue. In specimens from diabetic subjects, intense immunohistochemical staining for type VIII collagen was detected in mast cells, on periglomerular fibres and in perivascular and interstitial sites. The expression of type VIII collagen in periglomerular and interstitial sites coincided with that of alpha smooth muscle actin, a marker for myofibroblastic differentiation, mRNA for type VIII collagen was detected by reverse transcriptase-polymerase chain reaction in diabetic nephropathy and in a human mast cell line. By in situ hybridisation the transcripts for type VIII collagen were localised to renal mast cells. The increased number of mast cells and the elevated type VIII collagen deposition in human diabetic nephropathy provides a potential link between the extracellular matrix accumulation and the fibrosis observed in this condition. [Diabetologia (1996[Diabetologia ( ) 39: 1215[Diabetologia ( -1222

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Section: Discussionsupporting

confidence: 53%

mentioning

confidence: 99%

Mast cells and type VIII collagen in human diabetic nephropathy

Rüger¹,

Hasan²,

Greenhill³

et al. 1996

Diabetologia

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“…26 Increased expression of perlecan has been described in various kidney diseases including diabetic nephropathy, 27,28 membranous nephropathy, 29,30 minimal change nephrotic syndrome, 31 and diffuse mesangial sclerosis. 32 In addition, accumulation of collagen VI has also been described in various diseases including diabetic nephropathy, 33 diffuse mesangial sclerosis, 32 and membranous glomerulonephritis. 34 Perlecan and ␣1(VI)/␣5(IV) collagen are both located on the endothelial side of the GBM, limited to focal accumulations, 31 and to the mesangial matrix.…”

Section: Discussionmentioning

confidence: 99%

Antibody Response Against Perlecan and Collagen Types IV and VI in Chronic Renal Allograft Rejection in the Rat

Joosten

Dixhoorn

Borrias

et al. 2002

The American Journal of Pathology

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Chronic rejection is the leading cause of late renal transplant failure. Various structural lesions are observed in grafts undergoing chronic rejection including glomerular basement membrane (GBM) duplications. The well-established Fisher (F344) to Lewis (LEW) rat renal transplant model for chronic rejection was used to assess the presence and role of the humoral immune response against graft antigens during chronic rejection. LEW recipients of F344 allografts develop transplant glomerulopathy and produce IgG1 antibodies directed against F344 GBM preparations that are detectable 3 weeks after transplantation. Glomerular IgG1 deposition was observed that in vitro co-localized with a rabbit anti-rat GBM antiserum in rejecting F344 grafts; elution experiments of isolated glomeruli yielded IgG1 antibodies reactive in vitro with F344 GBM, but not LEW GBM. 1 The glomeruli may show a myriad of lesions, including chronic transplant glomerulopathy, which is characterized by duplication of the glomerular basement membrane (GBM) with interposition of electron-lucent material.2,3 Transplant glomerulopathy is observed in up to 20% of kidney grafts with CR. 4 It has been postulated that CR results from immune reactions of the recipient against yet poorly defined antigens exposed in the graft. 5 Nonimmune factors, such as hypertension or ischemia/reperfusion injury, may lead to unmasking or alteration of graft antigen(s).1 In syngeneic transplants with comparable degrees of nonimmune injury, CR does not develop within the same time span compared with allogeneic grafts, underlining the importance of immunological mechanisms.6 -8 We hypothesize that immune reactions such as antibody formation after previous damage play a role in the perpetuation of CR in renal allografts. In a mouse model of chronic cardiac graft rejection, antibodies are crucial for disease development.7 Immunoglobulin heavy chain (IGH) knockout mice that receive a cardiac allograft do not develop CR in contrast to immunoglobulin heavy chain wild-type mice.7 Moreover, transfer of posttransplantation (Tx) IgG antibodies or antigen-reactive immune serum into transplanted SCID mice results in transplant atherosclerosis. 6,8 A well-established model to study CR in renal allografts is the F344 to LEW rat model. All LEW recipients of F344 grafts develop acute rejection at approximately day 30 resulting in 50% graft loss. The surviving animals show histopathological and functional characteristics of CR from day 50. The reverse combination, ie, LEW kidneys transplanted into F344 rats all exhibit long-term surviving kidney grafts in the absence of histological abnormalities, despite early acute rejection episodes. In this model, antibody responses specific for lymph node-derived lymphocytes have been described. 9 These antibodies disappeared at 8 weeks after Tx and were described to

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“…Increased expression of CVI is found in the ECM of melanomas or gliomas (27,28) or in chronic fibrotic conditions (54,55). Thus, CVI-content is increased 10-fold in fibrotic livers, and CVI serum levels are highly elevated in adults and children with advanced renal and hepatic fibrosis (55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

Soluble Collagen VI Drives Serum-starved Fibroblasts through S Phase and Prevents Apoptosis via Down-regulation of Bax

Rühl¹,

Sahin²,

Johannsen³

et al. 1999

Journal of Biological Chemistry

107

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We previously showed that soluble, pepsin-solubilized collagen VI increases de novo DNA synthesis in serumstarved HT1080 and 3T3 fibroblasts up to 100-fold compared with soluble collagen I, reaching 80% of the stimulation caused by 10% fetal calf serum. Here we show that collagen VI also inhibits apoptotic cell death in serum-starved cells as evidenced by morphological criteria, DNA laddering, complementary apoptosis assays (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, enzyme-linked immunosorbent assay, and fluorescence-activated cell sorting), and quantification of apoptosis-regulating proteins. In the presence of starving medium alone or collagen I, the proapoptotic Bax was up-regulated 2-2.5-fold, compared with soluble collagen VI and fetal calf serum, whereas levels of the antiapoptotic Bcl-2 protein remained unaffected. In accordance with its potent stimulation of DNA synthesis, soluble collagen VI carries serum-starved HT1080 and Balb 3T3 fibroblasts through G 2 as shown by fluorescence-activated cell sorting analysis, whereas cells exposed to medium and collagen I where arrested at G 1 -S. This was accompanied by a 2-3-fold increase in cyclin A, B, and D1 protein expression. Collagen VI-induced inhibition of apoptotic cell death may be operative during embryogenesis, wound healing, and fibrosis when elevated tissue and blood levels of collagen VI are observed, thus initiating a feedback loop of mesenchymal cell activation and proliferation.

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Immunohistochemical localization of collagen VI in diabetic glomeruli

Cited by 69 publications

References 33 publications

Mast cells and type VIII collagen in human diabetic nephropathy

Mast cells and type VIII collagen in human diabetic nephropathy

Antibody Response Against Perlecan and Collagen Types IV and VI in Chronic Renal Allograft Rejection in the Rat

Soluble Collagen VI Drives Serum-starved Fibroblasts through S Phase and Prevents Apoptosis via Down-regulation of Bax

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