646000 四川 泸州,西南医科大学附属医院整形烧伤外科, 国家临床重点建设专科, 创面修复与再生实验室
Received:05 January 2021,
Revised:2021-02-26,
Published:15 June 2021
移动端阅览
Yuting YANG, Lan LIU, Xiaobin DING, et al. Heterogeneity: epidermal morphology and expression of epithelial-mesenchymal transition-related factors between the center and margin of keloids[J]. Journal of Third Military Medical University, 2021, 43(11): 1025-1031.
Yuting YANG, Lan LIU, Xiaobin DING, et al. Heterogeneity: epidermal morphology and expression of epithelial-mesenchymal transition-related factors between the center and margin of keloids[J]. Journal of Third Military Medical University, 2021, 43(11): 1025-1031. DOI: 10.16016/j.1000-5404.202101043.
目的
2
通过对比分析瘢痕疙瘩边缘、中心及正常皮肤E-cadherin、Vimentin、血管内皮生长因子(vascular endothelial growth factor,VEGF)和缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α) 表达以及表皮层组织学上的差异,探讨瘢痕疙瘩侵袭性生长的原因。
方法
2
纳入2019年10月至2020年8月本院整形烧伤外科行瘢痕疙瘩切除手术的患者16例,共16个瘢痕疙瘩组织,以及需要进行部分正常皮肤切除的手术患者9例,共9个正常皮肤组织,使用HE染色观察瘢痕疙瘩边缘、中心及正常皮肤组织形态,免疫组化染色和Western blot检测E-cadherin、Vimentin、VEGF和HIF-1α蛋白在不同组织中的表达。
结果
2
瘢痕疙瘩表皮层存在明显异常及异质性,边缘表皮层呈细分枝状并明显深入真皮,形成较深的犬牙交错状表现,而中心表皮层增厚扁平;免疫组化及Western blot检测结果均显示:瘢痕疙瘩边缘和中心表皮层E-cadherin表达显著低于正常皮肤(
P
<
0.05),且边缘显著低于中心(
P
<
0.05);Vimentin、HIF-1α、VEGF表达显著高于正常皮肤(
P
<
0.05),边缘显著高于中心(
P
<
0.05)。
结论
2
瘢痕疙瘩边缘表皮呈分枝状并明显向真皮层延伸,上皮间质转化活跃,HIF-1α及VEGF高表达且微血管丰富,可能与瘢痕疙瘩边缘的侵袭性生长相关,HIF-1α可能是其中的关键因子。
Objective
2
To investigate the causes of keloid invasive growth by comparing the expressional differences of E-cadherin
vimentin
vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1α)
and the epidermal histological differences among keloid marginal region
central region and normal skin.
Methods
2
This study enrolled 16 patients undergoing keloid resection in our department from October 2019 to August 2020
with a total of 16 keloid tissues
and 9 patients who required partial normal skin resection during the operation
with a total of 9 normal skin tissues. Hematoxylin and eosin (H&E) staining was used to observe the tissue morphology
and immunohistochemical staining and Western blot assay were used to detect the expression of E-cadherin
vimentin
VEGF and HIF-1α in above tissues.
Results
2
There was obvious abnormality and heterogeneity in the epidermal layer of keloids. The marginal epidermal subdivided into fine-branch-like and then clearly penetrated into the dermis
forming a houndstooth-like appearance
while the central epidermal became thick and flat; Immunohistochemical staining and Weste
rn blot assay showed that the expression level of E-cadherin was significantly weaker in the marginal and central epidermal of keloid tissue than in the normal skin (
P
<
0.05)
with that in the margin weaker than the center (
P
<
0.05); The levels of vimentin
HIF-1α and VEGF were significantly higher in the keloid tissue than normal skin (
P
<
0.05)
and those in the margin took the highest (
P
<
0.05).
Conclusion
2
Marginal epidermis of keloid clearly extends to the dermis in branched appearance
with active epithelium-to-mesenchymal transition (EMT)
highly expressed HIF-1α
VEGF and abundant microvessels. The underlying mechanism may be related to the aggressive growth of the keloid edge
and HIF-1α might be the key factor.
NANGOLE F W, AGAK G W. Keloid pathophysiology: fibroblast or inflammatory disorders?[J]. JPRAS Open, 2019, 22: 44-54.
LU F, GAO J, OGAWA R, et al . Biological differences between fibroblasts derived from peripheral and central areas of keloid tissues[J ] . Plast Reconstr Surg, 2007, 120(3): 625-630.
LIMANDJAJA G C, NIESSEN F B, SCHEPER R J, et al . The keloid disorder: heterogeneity, histopathology, mechanisms and models[J ] . Front Cell Dev Biol, 2020, 8: 360.
LEMPERLE G, SCHIERLE J, KITOGA K E, et al . Keloids: which types can be excised without risk of recurrence? a new clinical classification[J ] . Plast Reconstr Surg Glob Open, 2020, 8(3): e2582.
SYED F, AHMADI E, IQBAL S A, et al . Fibroblasts from the growing margin of keloid scars produce higher levels of collagen Ⅰ and Ⅲ compared with intralesional and extralesional sites: clinical implications for lesional site-directed therapy[J ] . Br J Dermatol, 2011, 164(1): 83-96.
JIAO H, ZHANG T R, FAN J C, et al . The superficial dermis may initiate keloid formation: histological analysis of the keloid dermis at different depths[J ] . Front Physiol, 2017, 8: 885.
HAHN J M, MCFARLAND K L, COMBS K A, et al . Partial epithelial-mesenchymal transition in keloid scars: regulation of keloid keratinocyte gene expression by transforming growth factor-β1[J ] . Burn Trauma, 2016, 4(1): 30.
MA X, CHEN J, XU B, et al . Keloid-derived keratinocytes acquire a fibroblast-like appearance and an enhanced invasive capacity in a hypoxic microenvironment in vitro [J ] . Int J Mol Med, 2015, 35(5): 1246-1256..
KUWAHARA H, TOSA M, EGAWA S, et al . Examination of epithelial mesenchymal transition in keloid tissues and possibility of keloid therapy target[J ] . Plast Reconstr Surg Glob Open, 2016, 4(11): e1138.
TAN S, KHUMALO N, BAYAT A. Understanding keloid pathobiology from a quasi-neoplastic perspective: less of a scar and more of a chronic inflammatory disease with cancer-like tendencies[J]. Front Immunol, 2019, 10: 1810.
XU G, ZHAO H, XU J, et al . Hard antler extract inhibits invasion and epithelial-mesenchymal transition of triple-negative and Her-2 + breast cancer cells by attenuating nuclear factor-κB signaling[J ] . J Ethnopharmacol , 2021, 269: 113705..
TAM S Y, WU V W C, LAW H K W. Hypoxia-induced epithelial-mesenchymal transition in cancers: HIF-1α and beyond[J]. Front Oncol, 2020, 10: 486.
PARK J H, MOON M, KIM J S, et al . TOPK mediates hypoxia-induced epithelial-mesenchymal transition and the invasion of nonsmall-cell lung cancer cells via the HIF-1α/snail axis[J ] . Biochem Biophys Res Commun, 2021, 534: 941-949.
BEKES I, FRIEDL T W, KÖHLER T, et al . Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?[J ] . Mol Cancer, 2016, 15: 13.
李红雨, 余亚南, 胡晓静, 等. 上皮性卵巢癌组织中TGF-β1, FOXQ1, VEGF, E-cad, N-cad的表达及意义[J]. 山东医药, 2017, 57(2): 91-94.
LI H Y, YU Y N, HU X J, et al . The expression and significance of TGF-β1, FOXQ1, VEGF, E-cad, N-cad in epithelial ovarian cancer[J ] . Shandong Med J, 2017, 57(2): 91-94.
LIMANDJAJA G C, BELIEN J M, SCHEPER R J, et al . Hypertrophi c and keloid scars fail to progress from the CD34 - /α-smooth muscle actin (α-SMA) + immature scar phenotype and show gradient differences in α-SMA and p16 expression[J ] . Br J Dermatol, 2020, 182(4): 974-986..
YANG C E, MOON S J, KIM S J, et al . Epithelial-mesenchymal transition in keloid tissue[J ] . Arch Plast Surg, 2018, 45(6): 600-601.
LIMANDJAJA G C, VAN DEN BROEK L J, WAAIJMAN T, et al . Increased epidermal thickness and abnormal epidermal differentiation in keloid scars[J ] . Br J Dermatol, 2017, 176(1): 116-126.
JUMPER N, PAUS R, BAYAT A. Functional histopathology of keloid disease[J]. Histol Histopathol, 2015, 30(9): 1033-1057.
ZHANG M, LIU S, GUAN E, et al . Hyperbaric oxygen therapy can ameliorate the EMT phenomenon in keloid tissue[J ] . Medicine (Baltimore), 2018, 97(29): e11529.
吴晓燕, 刘林盛, 罗志广, 等. 病理性瘢痕患者HIF-1α、VEGF、MMP-2的表达及临床意义[J]. 中国医师杂志, 2018, 20(7): 1025-1028, 1031.
WU X Y, LIN L S, LUO Z G, et al . Expression and clinical significance of HIF-1α, VEGF, MMP-2 in patients with pathological scar[J ] . J Chin Physician, 2018, 20(7): 1025-1028, 1031.
LEI R, ZHANG S, WANG Y, et al . Metformin inhibits epithelial-to-mesenchymal transition of keloid fibroblasts via the HIF-1α/PKM2 signaling pathway[J ] . Int J Med Sci, 2019, 16(7): 960-966..
ZHANG M, LIU S, Guan E, et al . Hyperbaric oxygen therapy can ameliorate the EMT phenomenon in keloid tissue[J ] . Medicine (Baltimore), 2018, 97(29): e115.
CHIN M S, FRENIERE B B, BONNEY C F, et al . Skin perfusion and oxygenation changes in radiation fibrosis[J ] . Plast Reconstr Surg, 2013, 131(4): 707-716.
ICHIOKA S, ANDO T, SHIBATA M, et al . Oxygen consumption of keloids and hypertrophic scars[J ] . Ann Plast Surg, 2008, 60(2): 194-197.
SONG K X, LIU S, ZHANG M Z, et al . Hyperbaric oxygen therapy improves the effect of keloid surgery and radiotherapy by reducing the recurrence rate[J ] . J Zhejiang UnivSci B, 2018, 19(11): 853-862.
TOUCHI R, UEDA K, KUROKAWA N, et al . Central regions of keloids are severely ischaemic[J ] . J Plast Reconstr Aesthet Surg, 2016, 69(2): e35-e41.
KUROKAWA N, UEDA K, TSUJI M. Study of microvascular structure in keloid and hypertrophic scars: density ofmicrovessels and the efficacy of three-dimensional vascular imaging[J]. J Plast Surg Hand Surg, 2010, 44(6): 272-277.
ZHENG J, SONG F, LU S L, et al . Dynamic hypoxia in scar tissue during human hypertrophic scar progression[J ] . Dermatol Surg, 2014, 40(5): 511-518.
JAIDEE R, KONGPETCH S, SENGGUNPRAI L, et al . Phenformin inhibits proliferation, invasion, and angiogenesis of cholangiocarcinoma cells via AMPK-mTOR and HIF-1A pathways[J ] . Naunyn-Schmiedeberg's Arch Pharmacol, 2020, 393(9): 1681-1690..
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