Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients.

Peissel, Bernard; Li, Geng; Kalluri, Raghu; Kashtan, Clifford E.; Rennke, Helmut G.; Gallo, Gloria; Yoshioka, Kazuo; Sun, Mae Jane; Hudson, Billy G.; Neilson, Eric G.

doi:10.1172/jci118241

Cited by 105 publications

(77 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…a6(IV) chain was seen in the distal tubular segment and BCBM. This is in good agreement with the earlier results on both rat and human kidney (Miner and Sanes, 1994;Ninomiya et al, 1995;Peissel et al, 1995;Yoshioka et al, 1994).…”

Section: Discussionsupporting

confidence: 93%

“…Rabbit antisera raised against collagen a3(IV), a4(IV) and a5(IV) were characterized by Miner and Sanes (1994) and that raised against collagen a6(IV) by Peissel et al (1995). MAb M3F7 to a1, a2(IV) was described earlier (Foellmer et al, 1983) and was purchased from Developmental Studies Hybridoma Bank (University of Iowa, IA).…”

Section: Antibodies and Immunohistochemistrymentioning

confidence: 99%

“…In human kidney a3(IV) chain was found in mature GBM, BCBM and distal tubular BM (Mårtensson et al, 1995) and a5(IV) chain in developing and adult GBM and in mature BCBM (Yoshioka et al, 1994). a6(IV) chain is present in the BCBM, distal tubular BM and collecting ducts in rats and humans (Ninomiya et al, 1995;Peissel et al, 1995). However, the expression of a3(IV) and a4(IV) chains in fetal human kidney and a4(IV) in mature human kidney remains to be elucidated.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Expression of type IV collagen α1(IV)–α6(IV) polypeptides in normal and developing human kidney and in renal cell carcinomas and oncocytomas

et al. 1997

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

Section: Antibodies and Immunohistochemistrymentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Expression of type IV collagen α1(IV)–α6(IV) polypeptides in normal and developing human kidney and in renal cell carcinomas and oncocytomas

et al. 1997

View full text Add to dashboard Cite

“…In the human and rodent kidney, immunohistochemical studies have shown a low-level expression of ␣1(IV) to ␣2(IV) in mature GBM whereas the ␣3(IV) to ␣5(IV) chains are highly expressed. [22][23][24][25][26][27] Little is known about the different isoforms of triple-helical type IV collagen molecules, 5,28 and their supramolecular organization in the different basement membranes. However, different subpopulations of NC1 hexamers, which reflect the association of two triple-helical molecules within the type IV collagen network, have been described recently in GBM as well as in other basement membranes.…”

mentioning

confidence: 99%

Glomerular Expression of Type IV Collagen Chains in Normal and X-Linked Alport Syndrome Kidneys

Heidet

Cai

Guicharnaud

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

Alport syndrome is an inherited nephropathy characterized by alterations of the glomerular basement membrane because of mutations in type IV collagen genes. COL4A5 mutations, causing X-linked Alport syndrome, frequently result in the loss of the ␣5 chains of type IV collagen in basement membranes. This is associated with the absence of the ␣3(IV) and ␣4(IV) chains and increased amounts of ␣1(IV) and ␣2(IV) in glomerular basement membranes. The mechanisms resulting in such a configuration are still controversial and are of fundamental importance for understanding the pathology of the disease and for considering gene therapy. In this article we studied, for the first time, type IV collagen expression in kidneys from X-linked Alport syndrome patients, using in situ hybridization and immunohistochemistry. We show that, independent of the type of mutation and of the level of COL4A5 transcription, both COL4A3 and COL4A4 genes are actively transcribed in podocytes. Moreover, using immunofluorescence amplification, we were able to demonstrate that the ␣3 chain of type IV collagen was present in the podocytes of all patients. Finally, the ␣1(IV) chain, which accumulates within glomerular basement membranes, was found to be synthesized by mesangial/endothelial cells. These results strongly suggest that, contrary to what has been found in dogs affected with X-linked Alport syndrome, there is no transcriptional co-regulation of COL4A3, COL4A4, and COL4A5 genes in humans, and that the absence of ␣3(IV) to ␣5(IV) in glomerular basement membranes in the patients results from events downstream of transcription, RNA processing, and protein synthesis.

show abstract

“…Type IV collagen is assembled from a family of distinct ␣-chains designated ␣1 to ␣6, which are encoded by six different genes, COL4A1 to COL4A6, respectively. 7 The glomerular basement membrane (GBM) is composed of the ␣1 to ␣5 chains, 8,9 which are assembled in triple helices that in turn selfassemble into supramolecular networks. Two distinct ␣1/ ␣2-containing and ␣3/␣4/␣5-containing networks have been identified at the biochemical level.…”

mentioning

confidence: 99%

The Inner Ear of Dogs with X-Linked Nephritis Provides Clues to the Pathogenesis of Hearing Loss in X-Linked Alport Syndrome

Harvey

Mount

Sado

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the ␣5 chain of type IV collagen lead to loss of the ␣3/␣4/␣5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen ␣-chains in the inner ear. By 1 month in normal adult dogs, the ␣3, ␣4, and ␣5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the ␣3/␣4/␣5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express ␣-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the ␣3/␣4/␣5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds.

show abstract

Comparative distribution of the alpha 1(IV), alpha 5(IV), and alpha 6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients.

Abstract: We have shown previously that the 5' ends of the genes for the ca5(IV) and ca6(IV) collagen chains lie head-to-head on

Cited by 105 publications

References 43 publications

Expression of type IV collagen α1(IV)–α6(IV) polypeptides in normal and developing human kidney and in renal cell carcinomas and oncocytomas

Expression of type IV collagen α1(IV)–α6(IV) polypeptides in normal and developing human kidney and in renal cell carcinomas and oncocytomas

Glomerular Expression of Type IV Collagen Chains in Normal and X-Linked Alport Syndrome Kidneys

The Inner Ear of Dogs with X-Linked Nephritis Provides Clues to the Pathogenesis of Hearing Loss in X-Linked Alport Syndrome

Contact Info

Product

Resources

About