GROWTH ABNORMALITIES IN CULTURED MESANGIAL CELLS FROM RATS WITH SPONTANEOUS GLOMERULOSCLEROSIS

Age-related glomerulosclerosis (GS) occurs in normotensive rats of the Milan strain (MNS), but not in genetically-matched hypertensive anima ls (MHS). Altered mesangial cell (MC) proliferation and matrix expansi on are common features of the glomerular scarring process. We evaluate d proliferation and matrix protein synthesis of cultured MC from MNS a nd MHS animals aged 1 and 8 months, that is, before and after the occu rrence of GS. [H-3]-thymidine (TdR) incorporation into DNA of MC from MNS rats stimulated by 10% FBS serum increased with donor aging from 1 15 +/- 6.0 to 176 +/- 15, P < 0.01 (% cpm/well over quiescent controls +/- SEM). Under the same experimental conditions, cell counts changed from 101 +/- 4.0 to 146 +/- 5.0, P < 0.01 (% cells/well over quiescen t controls). Additionally, cytosolic Ca2+ concentration ([Ca2+](i)) ri sed from 115 +/- 19 to 220 +/- 32 nM and from 112 +/- 24 to 734 +/- 13 6 nM when fura-2-loaded cells from young and old MNS rats, respectivel y, were stimulated with 1% FBS. The rate of collagen production also i ncreased with donor age, as well as collagen IV and laminin B1 mRNA ex pression. In contrast, in MC from MHS rats both DNA synthesis and cell replication rate declined as function of donor age. No differences in the [Ca2+](i) responses to FBS were observed, nor collagen production changed with MHS rat senescence. We conclude that the age-associated decline of proliferative activity in MC from MHS animals could actuall y reflect a normal process of cell aging, possibly protecting from the occurrence of GS. At variance, in MNS rat-derived cells such physiolo gic process may be genetically altered. This may translate into an age -dependent hyperresponsiveness to growth stimuli, thereby facilitating the development of GS.