Pathological and molecular genetic studies on collagen VI deficient Ullrich's disease

VI型胶原缺乏型乌尔里希病的病理学和分子遗传学研究

• 批准号: 14570611
• 负责人: HIGUCHI Itsuro
• 金额: $ 1.98万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570611/
• 关键词: Ullrich's disease; Extracellular matrix; Collagen VI; Proteoglycan; Fibronectin receptor; collagen VI; NGZproteoglycan; myosin heavy chain; fibronectin

Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints and hyperextensibility of the distal joints. Recently, we found a deficiency of collagen VI protein in skeletal muscle from two patients with Ullrich's disease.In this study, we performed electron microscopic and immunohistochemical investigations on biopsied skeletal muscles. We found electron microscopic abnormalities of skeletal muscle membrane and capillaries.Furthermore we found a marked reduction of fibronectin receptors in the extracellular matrix of skin and cultured fibroblasts of these patients and found that very small muscle fibers in the patients with Ullrich's disease showed poor expression of developmental myosin heavy chain and thrombomodulin.These findings suggest that abnormality of cell adhesion and abnormal regeneration or maturation processes are involved in the pathogenesis of dystrophic muscle changes at least in the advanced stage of Ullrich's disease.

乌尔里希氏病患者有全身性肌肉无力、近端关节多处挛缩和远端关节过度伸展。最近，我们发现两名乌尔里希病患者的骨骼肌中缺乏胶原蛋白 VI 蛋白。在这项研究中，我们对活检的骨骼肌进行了电子显微镜和免疫组织化学研究。我们发现骨骼肌膜和毛细血管的电镜异常。此外，我们发现这些患者的皮肤和培养的成纤维细胞的细胞外基质中纤连蛋白受体显着减少，并发现乌尔里希病患者的非常小的肌纤维显示发育性肌球蛋白重链和血栓调节蛋白的表达较差。这些发现表明 至少在乌尔里希病晚期，细胞粘附异常和异常再生或成熟过程参与营养不良性肌肉变化的发病机制。

项目成果

Hu J, Higuchi I, Shiraishi T, Suehara M, Niiyama T, Horikiri T, Uchida Y, Saito A, Osame M.: "Fibronectin receptor reduction in skin and fibroblasts of patients with Ullrich's disease."Muscle Nerve. 26. 696-701 (2002)

Hu J，Higuchi I，Shiraishi T，Suehara M，Niiyama T，Horikiri T，Uchida Y，Saito A，Osame M.：“乌尔里希病患者皮肤和成纤维细胞中纤连蛋白受体减少。”肌肉神经。

Higuchi I, Horikiri T, Niiyama T, Suehara M, Shiraishi T, Hu J, Uchida Y, Saito A, Nakagawa M, Arimura K, Osame M.: "Pathological characteristics of skeletal muscle in Ullrich's disease with collagen VI deficiency."Neuromuscul Disord. 13. 310-316 (2003)

Higuchi I、Horikiri T、Niiyama T、Suehara M、Shiraishi T、Hu J、Uchida Y、Saito A、Nakakawa M、Arimura K、Osame M.：“伴有 VI 型胶原蛋白缺乏的乌尔里希病骨骼肌的病理特征。”

Hu J et al.: "Fibronectin receptor reduction in skin and fibroblasts of patients with Ullrich's disease."Muscle Nerve. 26(5). 696-701 (2002)

Hu J 等人：“乌尔里希病患者皮肤和成纤维细胞中纤连蛋白受体减少。”肌肉神经。

Niiyama T, Higuchi I et al.: "Capillary changes in skeletal muscle of patients with Ullrich's disease with collagen VI deficiency."Acta Neuropathol. 106. 137-142 (2003)

Niiyama T、Higuchi I 等人：“伴有 VI 型胶原蛋白缺乏的乌尔里希病患者骨骼肌中的毛细血管变化。”Acta Neuropathol。

Niiyama T et al.: "Capillary changes in skeletal muscle of patients with Ullrich's disease with collagen VI deficiency."Acta Neuropathol. 106(2). 137-142 (2003)

Niiyama T 等人：“伴有 VI 型胶原蛋白缺乏的乌尔里希氏病患者骨骼肌毛细血管变化。”Acta Neuropathol。