From the Gillies McIndoe Research Institute; and the Wellington Regional Plastic, Maxillofacial, and Burns Unit, Hutt Hospital.
Plast Reconstr Surg. 2019 Aug;144(2):372-384. doi: 10.1097/PRS.0000000000005867.
We investigated expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 by the embryonic stem cell-like population on the endothelium of the microvessels and perivascular cells within keloid-associated lymphoid tissues.
Immunohistochemical staining for prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 was performed on 11 formalin-fixed, paraffin-embedded sections of keloid tissue samples. Immunofluorescence staining was performed on three keloid tissue samples by co-staining with OCT4, CD34, ERG, and tryptase. Real-time quantitative polymerase chain reaction was performed on five keloid tissue samples and four keloid-derived primary cell lines. Western blotting was performed on the four keloid-derived primary cell lines for mRNA and protein expression of these proteins, respectively.
Immunohistochemical and immunofluorescence staining showed expression of prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 in all 11 keloid tissue samples. Prorenin receptor and angiotensin II receptor 1 were expressed on the endothelium and the pericyte layer of the microvessels and perivascular cells, angiotensin II receptor 2 was localized to the endothelium of the microvessels and the tryptase-positive perivascular cells, and angiotensin-converting enzyme was localized to the endothelium of the microvessel, within the keloid-associated lymphoid tissues. Real-time quantitative polymerase chain reaction showed transcripts of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid tissue samples and keloid-derived primary cell lines, whereas angiotensin II receptor 2 was detected in keloid tissue samples only. Western blotting confirmed the presence of prorenin receptor, angiotensin-converting enzyme, and angiotensin II receptor 1 in the keloid-derived primary cell lines.
Prorenin receptor, angiotensin-converting enzyme, angiotensin II receptor 1, and angiotensin II receptor 2 were expressed by the embryonic stem cell-like population within the keloid-associated lymphoid tissues, suggesting that this primitive population may be a potential therapeutic target by modulation of the renin-angiotensin system.
我们研究了胚胎干细胞样群体在微脉管内皮细胞和瘢痕相关淋巴组织中的血管周细胞上表达的前胰蛋白酶受体、血管紧张素转换酶、血管紧张素 II 受体 1 和血管紧张素 II 受体 2。
对 11 例福尔马林固定、石蜡包埋的瘢痕组织样本进行前胰蛋白酶受体、血管紧张素转换酶、血管紧张素 II 受体 1 和血管紧张素 II 受体 2 的免疫组织化学染色。对 3 例瘢痕组织样本进行免疫荧光染色，并用 OCT4、CD34、ERG 和胰蛋白酶进行共染色。对 5 例瘢痕组织样本和 4 例瘢痕衍生原代细胞系进行实时定量聚合酶链反应。对 4 例瘢痕衍生原代细胞系进行 Western blot 分析，以检测这些蛋白的 mRNA 和蛋白表达。
免疫组织化学和免疫荧光染色显示，所有 11 例瘢痕组织样本均表达前胰蛋白酶受体、血管紧张素转换酶、血管紧张素 II 受体 1 和血管紧张素 II 受体 2。前胰蛋白酶受体和血管紧张素 II 受体 1 表达于微脉管内皮细胞和血管周细胞的周细胞层，血管紧张素 II 受体 2 定位于微脉管内皮细胞和胰蛋白酶阳性的血管周细胞，血管紧张素转换酶定位于微脉管内皮细胞，位于瘢痕相关淋巴组织内。实时定量聚合酶链反应显示，前胰蛋白酶受体、血管紧张素转换酶和血管紧张素 II 受体 1 的转录本存在于瘢痕组织样本和瘢痕衍生原代细胞系中，而血管紧张素 II 受体 2 仅存在于瘢痕组织样本中。Western blot 证实，前胰蛋白酶受体、血管紧张素转换酶和血管紧张素 II 受体 1 存在于瘢痕衍生原代细胞系中。
前胰蛋白酶受体、血管紧张素转换酶、血管紧张素 II 受体 1 和血管紧张素 II 受体 2 表达于瘢痕相关淋巴组织中的胚胎干细胞样群体，提示该原始群体可能是通过调节肾素-血管紧张素系统的潜在治疗靶点。
