title: Expression of TLR4 protein is reduced in chronic renal failure: evidence from an experimental model of nephron reduction.
abstract: Toll-like receptor 4 (TLR4) signaling is involved in various acute and chronic renal lesions and contributes to inflammation and fibrosis in several organs; the latter are important determinants to the progression of chronic kidney disease (CKD). We aimed to assess TLR4 expression in progressive CKD and relate it to severity of kidney damage, using an experimental nephron reduction model. Male Wistar rats were subjected to subtotal nephrectomy using the ligation technique, after 12 weeks of observation, serum creatinine and proteinuria were determined, animals were sacrificed, glomerulosclerosis and interstitial scarring were quantified histologically, and TLR4 expression was assessed by immunohistochemistry. Sham-operated rats served as controls. Case animals had significantly higher creatinine, proteinuria, glomerulosclerosis and tubulointerstitial involvement. TLR4 expression was prominent in proximal tubes, less staining was observed on infiltrating inflammatory cells. Percentage of TLR4-positive tubes was reduced in the subtotal nephrectomy animals, when compared to controls (0.67±0.09 versus 0.79±0.07, p=0.003). Percentage of TLR4-positive tubes correlated inversely to markers of kidney damage: to proteinuria (r=-0.55, p=0.02), serum creatinine (r=-0.53, p=0.01); percentage of glomeruli with glomerulosclerosis (r=-0.54, p=0.01) and tubulointerstitial score (r=-0.36, p=0.01). As TLR4 staining appears in tubular casts only in nephrectomy animals, shedding from damaged tubular cells is a very likely explanation for the reduced TLR4 expression in the kidneys of subjects with experimental nephron reduction.
authors.affiliation: Department of Nephrology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania; inakacso@yahoo.com.
authors.forename: Ina Maria
authors.initials: IM
authors.lastname: Kacsó
authors.forename: Gabriel Mircea
authors.initials: GM
authors.lastname: Borza
authors.forename: Cătălin C
authors.initials: CC
authors.lastname: Ciuce
authors.forename: Andrei
authors.initials: A
authors.lastname: Bîrsan
authors.forename: Raluca Cristina
authors.initials: RC
authors.lastname: Apostu
authors.forename: George Călin
authors.initials: GC
authors.lastname: Dindelegan
authors.forename: Cosmina Ioana
authors.initials: CI
authors.lastname: Bondor
authors.forename: Alina Ramona
authors.initials: AR
authors.lastname: Potra
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Cornel
authors.initials: C
authors.lastname: Cătoi
mesh_terms: D000818:Animals; D005355:Fibrosis / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D009399:Nephrons / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4