INTRAGLOMERULAR PRESSURE AND MESANGIAL STRETCHING STIMULATE EXTRACELLULAR-MATRIX FORMATION IN THE RAT
INTRAGLOMERULAR PRESSURE AND MESANGIAL STRETCHING STIMULATE EXTRACELLULAR-MATRIX FORMATION IN THE RAT
复制标题
DOI：
10.1172/jci116071
复制
发表时间：
1992-11-01
影响因子：
15.9
通讯作者：
HOLCOMB, MA
中科院分区：
文献类型：
--
作者：
RISER, BL;CORTES, P;HOLCOMB, MA
为了明确肾小球高血压和肥大与系膜细胞外基质（ECM）沉积的相互作用，我们研究了肾小球毛细血管扩张和系膜细胞拉伸对ECM合成的影响。在体外以增加流量灌注的微解剖大鼠肾小球体积（V(g)）被量化，并与近端肾小球内压力（PIP）相关。肾小球顺应性，用PIP和V(g)之间正线性关系的斜率表示为7.68 X 10(3) mum3/mmHg。总V(g)增量（PIP 0-150 mmHg）为1.162 × 10(6) mum3或61% （n = 13）。在PIP范围内，V(g)增加16%，相当于平均经毛细血管压差的病理生理极限。肾灌注对V(g)的组织学影响在体内灌注/固定的肾脏组织中也被注意到。经过循环拉伸的培养系膜细胞增加了蛋白质、总胶原和ECM关键成分（胶原IV、胶原I、层粘连蛋白、纤维连接蛋白）的合成。合成率受细胞生长和拉伸程度的影响。这些结果表明肾小球高血压引起的毛细血管扩张和系膜细胞的拉伸引起ECM的增加，而细胞生长和肾小球肥大加剧了ECM的产生。系膜扩张和肾小球硬化可能是机械和代谢力相互作用的结果。
To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (V(g)), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and V(g) was 7.68 X 10(3) mum3/mmHg. Total V(g) increment (PIP 0-150 mmHg) was 1.162 X 10(6) mum3 or 61% (n = 13). A 16% increase in V(g) was obtained over the PIP range equivalent to the pathophysiologial limits of mean transcapillary pressure difference. A similar effect of renal perfusion on V(g) was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.