PMID- 10792628 OWN - NLM STAT- MEDLINE DCOM- 20000601 LR - 20071114 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 57 IP - 5 DP - 2000 May TI - Glomerular type IV collagen in patients with diabetic nephropathy with and without additional glomerular disease. PG - 2084-92 AB - BACKGROUND: Type IV collagen is a constituent of mesangial matrix and is increased in amount in many forms of glomerular injury. METHODS: We performed renal biopsies in patients who (1) were donating a kidney to a relative (LRD, N = 6), (2) had diabetic glomerulopathy with or without nephrosclerosis (DM, N = 6), or (3) had diabetic glomerulopathy with a superimposed glomerular lesion (DM+, N = 5). Glomerular collagen alpha2(IV) and control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNAs were measured, and the former correlated with clinical and morphological data to assess its usefulness in reflecting glomerular injury. RESULTS: Collagen alpha2(IV) mRNA levels were lowest in LRD (2.9 +/- 0.6 attomol/glomerulus), higher in DM (5.9 +/- 1.6, P = 0.05), and highest in DM+ (12.7 +/- 2.8 attm/glomerulus, P < 0.05 vs. LRD and vs. DM). Control GAPDH mRNA levels were not significantly different (P > 0.05). Levels of proteinuria, serum creatinine, and glomerular size did not correlate with collagen alpha2(IV) mRNA levels. The fractional mesangial area and the fractional mesangial area occupied by type IV collagen were higher in both diabetic groups than in LRD (P < 10-6), but the intensity of type IV collagen staining in the diabetic patients was significantly less than that seen in the LRD (P < 0.01). In DM+ patients, extramesangial type IV collagen was present. Fractional mesangial area and glomerular collagen alpha2(IV) mRNA levels correlated (r = 0.45, P < 0.05). CONCLUSION: These data are consistent with a view of diabetic nephropathy as a lesion of increased alpha2 type IV collagen transcription, increased total amount of collagen present, but decreased mesangial density relative to other matrix molecules. These data further demonstrate that glomerular injury superimposed on diabetic nephropathy contributes to additional structural damage by inducing increased synthesis of type IV collagen at extramesangial sites. FAU - Adler, S G AU - Adler SG AD - Harbor-UCLA Research and Education Institute, Torrance, CA 90509, USA. sadler@rei.edu FAU - Feld, S AU - Feld S FAU - Striker, L AU - Striker L FAU - Striker, G AU - Striker G FAU - LaPage, J AU - LaPage J FAU - Esposito, C AU - Esposito C FAU - Aboulhosn, J AU - Aboulhosn J FAU - Barba, L AU - Barba L FAU - Cha, D R AU - Cha DR FAU - Nast, C C AU - Nast CC LA - eng GR - MO1 RR00425/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (RNA, Messenger) RN - 9007-34-5 (Collagen) SB - IM MH - Adult MH - Collagen/analysis/*genetics MH - Diabetic Nephropathies/*metabolism/pathology MH - Humans MH - Hypertrophy MH - Immunohistochemistry MH - In Situ Hybridization MH - Kidney Glomerulus/*metabolism/pathology MH - Middle Aged MH - RNA, Messenger/*analysis MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2000/05/03 09:00 MHDA- 2000/06/03 09:00 CRDT- 2000/05/03 09:00 PHST- 2000/05/03 09:00 [pubmed] PHST- 2000/06/03 09:00 [medline] PHST- 2000/05/03 09:00 [entrez] AID - S0085-2538(15)46961-3 [pii] AID - 10.1046/j.1523-1755.2000.00058.x [doi] PST - ppublish SO - Kidney Int. 2000 May;57(5):2084-92. doi: 10.1046/j.1523-1755.2000.00058.x.