Roles of PDGF receptor-beta in the structure and function of postnatal kidney glomerulus.

BACKGROUND

Mesangial cell functions are critically regulated by platelet-derived growth factor receptor (PDGFR)-β signals. In contrast to the well-established role of PDGFR-β in the development of kidney glomerulus, its role in adult kidney glomerulus remains controversial.

METHODS

We deleted the PDGFR-β gene postnatally using the Cre-loxP system and analysed the long-term effects of PDGFR-β inhibition on glomerular changes associated with ageing and subtotal nephrectomy.

RESULTS

Mice depleted of PDGFR-β (Deletant) survived without showing apparent abnormalities. In glomerulus of Deletant, mesangial PDGFR-β expression was decreased. The glomerular cell numbers were low, and the ageing-associated increment of mesangial matrix area was suppressed in Deletant as compared with control mice with conserved PDGFR-β expression (Floxed) at 48 weeks of age. At 2 weeks after subtotal nephrectomy, albuminuria and the elevation of blood urea nitrogen were aggravated in Deletant. At this time, Deletant showed specific glomerular changes that included many hypertrophic podocytes and collapsed capillaries. At 12 weeks after subtotal nephrectomy, the kidney function in Deletant restored to the level of Floxed; however, the Deletant glomeruli showed dilated capillaries, decreased cell number and reduced mesangial matrix area with less extended mesangial cell processes as compared with Floxed.

CONCLUSIONS

The long-term inhibition of mesangial PDGFR-β prevented age-related mesangial expansion. On the other hand, the kidney glomeruli with decreased PDGFR-β showed increased vulnerability to the acute nephron loss, and showed mesangial insufficiency in the following adaptive process.