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Growth factor and extracellular matrix in glomerulosclerosis

肾小球硬化中的生长因子和细胞外基质

基本信息

批准号：
09671186
负责人：
OSAWA Gengo
金额：
$ 1.79万
依托单位：
KAWASAKI UNIVERSITY OF MEDICAL WELFARE (1998)Kawasaki Medical School (1997)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671186/
关键词：
Podocyte TGF-B Cyclin-CDK cyclin kinase inhibitor (CKI) family p21 p27 Osteopontin Tenascin BMP7 糸球体荒廃像 Bowman嚢上皮細胞尿細管間質病変

项目摘要

Podocytes are mostly present in the late G1 phase of the cell cycle even in the proliferative state, and there is no increase in the number of cells. As for the cyclin kinase inhibitor (CKI) family, which suppresses shifting of the cell cycle from the G i to the S phase, p21 and p27 have been identified. Regarding the number of p27-positive cells in podocytes, changes due to administration of FGF2 were not observed, but an increase in p21-positive podocytes was noted. These findings suggest that the reason most podocytes remain in the late GL phase might be upregulation of p21. Furthermore, FGF2 induced podocyte injury related to the transit cell cycle. When two sets of PAN rats were compared, the number of BrdU-positive cells was clearly greater in the rats administered FGF2. This finding demonstrated that a few podocytes entered the DNA synthesis phase. The number of bi - or multi- nucleated podocytes was counted in these rats. Our hypothesis is that podocytes entering the S phase are associated with FGF2-idced cell damage. We have shown that TGF-B isoforms and receptors increase with the podocytes of various glomerular injury models. The smad family was recently isolated and identified in the signalling of TGF-B.Expression of the smad family was observed in the podocytes of various glomerular injury models. TGF-B increases the expression of p21 in certain cells in vitro. Taken together, increases in p21 expression in podocytes may be due to the upregulation of TGF-B.We propose that p21 protects podocytes against damage by preventing damaged cells from entering the cell cycle.

足细胞即使在增殖状态下也大多存在于细胞周期的晚期G1期，并且细胞数量没有增加。至于细胞周期蛋白激酶抑制剂（CKI）家族，其抑制细胞周期从G1期向S期的转变，已经鉴定了p21和p27。关于足细胞中p27阳性细胞的数量，未观察到由于施用FGF 2而引起的变化，但注意到p21阳性足细胞的增加。这些发现表明，大多数足细胞保持在GL晚期的原因可能是p21的上调。此外，FGF 2诱导足细胞损伤相关的过境细胞周期。当比较两组PAN大鼠时，施用FGF 2的大鼠中BrdU阳性细胞的数量明显更大。这一发现表明，少数足细胞进入DNA合成期。计算大鼠足细胞双核或多核数。我们的假设是足细胞进入S期与FGF 2介导的细胞损伤有关。我们已经表明，TGF-β亚型和受体增加与足细胞的各种肾小球损伤模型。smad家族最近被分离并鉴定为TGF-β的信号传导。在各种肾小球损伤模型的足细胞中观察到smad家族的表达。TGF-β在体外增加某些细胞中p21的表达。两者合计，足细胞中p21表达的增加可能是由于TGF-β的上调。我们建议，p21通过防止受损细胞进入细胞周期来保护足细胞免受损伤。