Progeria kidney has abnormal mesangial collagen distribution

Abstract

It has been suggested that progeria, a congenital disorder associated with clinical features that resemble premature aging, may be the result of a connective tissue abnormality. Although to date the clinical and pathologic features for 14 autopsied cases of progeria have been reported, details as to the renal changes in progeria are scanty. We investigated the histological features from a male and female with progeria who died aged 11 years and 20 years respectively. In our young male subject there was no glomerulosclerosis, while the kidney from the older subject showed focal renal scarring with focal glomerulosclerosis and associated tubular atrophy. Two small papillary adenomas were present within the renal cortex of the latter subject. In both cases non-sclerotic glomeruli were moderately enlarged with expansion of mesangial matrix. Immunohistochemical detection of collagens showed absence of collagen I and III within the mesangium of non-sclerotic glomeruli, while there was moderate to marked expression of collagen IV, V and VI. Collagen V is thought to be involved in matrix assembly while collagen VI probably has a regulatory role in extracellular matrix development and these are either not seen or are very weakly expressed in normal renal mesangium. The distribution of collagen within the mesangium of progeria kidney is evidence in support of the concept that progeria is a primary connective tissue disorder.

A comparison of pathomolecular markers of fibrosis and morphology in kidney from autopsies of African Americans and whites

“…This was done to prevent the advanced glomerulosclerosis of the more elderly [7] from producing an acquired nephron deficit in our studies on the relationship between nephron number and hypertension. Our study was also restricted for age because the State Department of Fig.…”

The evolution of collagen expression in sarcomatoid renal cell carcinoma

“…Sections were stained with hematoxylin and eosin, whereas serial sections were stained for collagen types I, III, IV, and V using goat polyclonal antibodies to human/ bovine collagen (Southern Biotechnology, Birmingham, AL) in respective dilutions of 1:200, 1:1000, 1:800, and 1:200 [10]. Sections were pretreated with 0.3% H 2 O 2 / methanol to block endogenous peroxidase activity.…”

“…Collagen type VI immunostaining was undertaken using rabbit antihuman polyclonal antibody (BioGenex, San Ramon, CA) at a dilution of 1:800 using the streptavidinbiotin method [10]. Biotinylated antirabbit antibody (Dako) at 1:50 dilution was used as the secondary antibody, and the reaction was visualized using liquid DAB with a hematoxylin counterstain.…”

Why Do Our Kidneys Get Old

“…It describes renal histopathology of 2 subjects who died from progeria. The younger subject who died aged 11 years had no glomerulosclerosis, while the kidney from the 20-year-old subject showed focal renal scarring with focal glomerulosclerosis and associated tubular atrophy, similar to that seen in physiological aging [28]. …”

“…The best studied of these premature aging syndromes, known as progeria, are due to mutations in helicases which are responsible for reading and checking and repairing the integrity of DNA. Although none of the progeroid syndromes exactly match physiological aging, studies of these syndromes are yielding clues to how DNA damage, which accumulates with age, may play a role in the aging process [28]. There is one report of kidney pathology related to progeria.…”