Inhibition of mitogenesis and c-fos induction in mesangial cells by heparin and heparan sulfates.
When rat renal mesangial cells (RMC) or vascular smooth muscle cells are released from quiescence by serum stimulation they express c-fos mRNA transiently at 30 to 60 minutes and progress in synchrony to S phase. Heparin causes significant suppression of [3H]-thymidine incorporation into DNA in S phase and a decrease and delay of entry of cells into S/G2. Added at the time of serum stimulation, heparin (1 microgram/ml or less) causes a decrease in the subsequent expression of c-fos mRNA in RMC, and a similar effect is observed with heparan sulfate chains isolated from RMC-cultures themselves. Although these cells internalize and degrade heparin, the timing of the maximal effect indicates an extracellular action of heparin. In keeping with this idea, 125I-heparin binds specifically to a single class of high affinity sites on the cell surface. The effect of heparin on c-fos induction may be independent of interaction with cytokines or cytokine receptors; its magnitude is not diminished when heparin-binding substances are removed from serum by heparin-Sepharose. Furthermore, direct activation of protein kinase C (PKC) with a phorbol ester in the absence of serum likewise induces c-fos and 1 microgram/ml heparin inhibits this response by 65%. Phorbol ester caused an increase in the proportion of histone H1-active PKC associated with the cell membrane fraction, from approximately 25% to 70% of total activity. Heparin affected neither the total activity of the kinase nor the proportion associated with the membrane. When PKC was inhibited with staurosporine, only very low levels of c-fos were induced by serum. We conclude that low concentrations of heparin and heparan sulfate suppress the mitogenic response of mesangial cells to serum and inhibit c-fos mRNA induction through an effect of cell surface-bound glycosaminoglycan on a signalling pathway downstream of PKC.
원문보기 무료다운로드 유료다운로드
- 유료 원문 정보가 존재하지 않습니다.
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 아래의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.