Hyaluronic acid production and CD44 expression in cultured dermal fibroblasts of patients with non‐insulin‐dependent diabetes mellitus with and without chronic ulcers on the lower extremity

Hyaluronic acid production and CD44 expression in cultured dermal fibroblasts of patients with non‐insulin‐dependent diabetes mellitus with and without chronic ulcers on the lower extremity
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伴或不伴下肢慢性溃疡的非胰岛素依赖型糖尿病患者培养的真皮成纤维细胞中透明质酸的产生和 CD44 的表达

DOI:
10.1111/j.1067-1927.2005.130209.x
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发表时间:
2005
影响因子:
2.9
通讯作者:
S. E. Podpryatov
S. E. Podpryatov
中科院分区:
医学3区
文献类型:
--
作者:
N. Yevdokimova;S. E. Podpryatov

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众所周知,透明质酸及其主要受体CD44参与了组织修复过程的调节,但它们在慢性糖尿病溃疡形成中的作用尚未被研究。透明质酸代谢和CD44的表达受乳酸的调节,乳酸的增加被认为影响了非胰岛素依赖型糖尿病成纤维细胞的特性。我们工作的目的是研究透明质酸和CD44在糖尿病创面异常愈合中的可能作用,以及乳酸对它们的调节。成纤维细胞来自四名有溃疡的非胰岛素依赖型糖尿病患者和四名无溃疡的非胰岛素依赖型糖尿病患者的未受伤皮肤,以及四名年龄匹配的健康志愿者。我们观察到两组糖尿病成纤维细胞都比对照组产生更多的L-乳酸(∼30%),并在透明质酸(∼28%)中掺入更多的~3H-氨基葡萄糖。与无溃疡组相比,糖尿病溃疡组成纤维细胞高分子量透明质酸在细胞外基质中的积聚显著增加(30.5%,p < 0.01),CD44表达显著增加(27.0%,p < 0.05)。外源L-乳酸对所有成纤维细胞系均呈剂量依赖关系,刺激中等浓度透明质酸蓄积(3.7倍)和CD44表达(1.5倍)。然而,糖尿病溃疡患者成纤维细胞对L-乳酸的CD44表达更敏感(1.4倍),而对L-乳酸的反应是细胞外基质中高相对分子质量的透明质酸积累增加(32.1%,p < 0.01)。我们认为糖尿病溃疡患者成纤维细胞的特性可能与这些患者对慢性溃疡的易感性增加有关。
It is well known that hyaluronic acid and its principal receptor, CD44, are implicated in the regulation of the tissue repair process, but their role in the formation of chronic diabetic ulcers has not been studied. Hyaluronic acid metabolism and CD44 expression are regulated by lactate, where their increased production is considered to affect the properties of fibroblasts in non‐insulin‐dependent diabetes mellitus. The aim of our work was to investigate the possible role of hyaluronic acid and CD44, and their regulation by lactate, in the abnormal wound healing of diabetes. Fibroblasts were derived from uninjured skin from four non‐insulin‐dependent diabetic patients with ulcers and four without ulcers; and from four healthy age‐matched volunteers. We observed that diabetic fibroblasts of both groups produced more L‐lactate (∼30%) and incorporated more 3H‐glucosamine into the medium hyaluronic acid (∼28%) than controls. Fibroblasts of the diabetic group with ulcers, unlike those of the group without ulcers, showed significant increases in the high molecular weight hyaluronic acid accumulation in the pericellular matrix (30.5%, p < 0.01) and CD44 expression (27.0%, p < 0.05). Exogenous L‐lactate dose‐dependently, and equally for all fibroblasts lines, stimulated the accumulation of medium hyaluronic acid (3.7‐fold) and CD44 expression (1.5‐fold). However, fibroblasts from diabetic patients with ulcers were more (1.4‐fold) sensitive to L‐lactate in terms of CD44 expression, and responded to L‐lactate by the increased accumulation of high molecular weight hyaluronic acid in the pericellular matrix (32.1%, p < 0.01). We propose that specific properties of fibroblasts from diabetic patients with ulcers may be involved in the increased susceptibility of these patients to chronic ulceration.
DOI: 10.1006/excr.2002.5508
发表时间: 2002-05-15
影响因子: 3.7
作者:
Stern, R;Shuster, S;Fromby, B
通讯作者: Fromby, B
DOI: 10.1016/0360-3016(94)00362-o
发表时间: 1995-02-01
影响因子: 7
作者:
RUTZ, HP;LITTLE, JB
通讯作者: LITTLE, JB