Institute of Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangdong 530001, Guangdong Province, China.
Traditional Chinese Medicine Department, The Second People's Hospital of Lianyungang, Lianyungang 222000, Jiangsu Province, China.
World J Gastroenterol. 2021 Oct 21;27(39):6615-6630. doi: 10.3748/wjg.v27.i39.6615.
Extracellular matrix (ECM) remodeling and stiffening, which are correlated with tumor malignancy, drives tumor development. However, the relationship between ECM remodeling and rat experimental model of 1,2-dimethylhyrazine (DMH)-induced colorectal cancer (CRC) imposed by cold and capsaicin exposure remains unclear.
To explore the effects of cold exposure and capsaicin on ECM remodeling and ECM enzymes in DMH-induced CRC.
For histopathological analysis, the sections of colon tissues were stained with hematoxylin and eosin, Masson's trichrome, Picrosirius red, and Weigert's Resorcin-Fuchsin to observe the remodeling of collagen and elastin. Additionally, the protein expression level of type I collagen (COL I), type 3 collagen (COL III0, elastin, matrix metalloproteinase (MMP) 1, MMP2, MMP9, and tissue-specific matrix metalloproteinase 1 (TIMP1) was assessed by immunohistochemistry. The messenger RNA (mRNA) levels of COL I, COL III, elastin, and lysyl oxidase-like-2 (LOXL2) in the colon tissues of rats was measured by reverse-transcriptase quantitative polymerase chain reaction.
Although no differences were observed in the proportion of adenomas, a trend towards the increase of invasive tumors was observed in the cold and capsaicin group. The cold exposure group had a metastasis rate compared with the other groups. Additionally, abnormal accumulation of both collagen and elastin was observed in the cold exposure and capsaicin group. Specifically, collagen quantitative analysis showed increased length, width, angle, and straightness compared with the DMH group. Collagen deposition and straightness were significantly increased in the cold exposure group compared with the capsaicin group. Cold exposure and capsaicin significantly increased the protein levels of COL I, elastin, and LOXL2 along with increases in their mRNA levels in the colon tissues compared with the DMH group, while COL III did not show a significant difference. Furthermore, in immunohistochemical evaluations, MMP1, MMP2, MMP9, and TIMP1 staining increased in the cold exposure and capsaicin group compared with the DMH group.
These results suggest that chronic cold and capsaicin exposure further increased the deposition of collagen and elastin in the colonic tissue. Increased COL I and elastin mRNA and protein levels expression may account for the enhanced ECM remodel and stiffness variations of colon tissue. The upregulated expression of the LOXL2 and physiological imbalance between MMP/TIMP activation and deactivation could contribute to the progression of the CRC resulting from cold and capsaicin exposure.
细胞外基质（ECM）的重塑和变硬与肿瘤恶性程度相关，推动了肿瘤的发展。然而，ECM 重塑与冷暴露和辣椒素暴露对 1,2-二甲基肼（DMH）诱导的大鼠结直肠癌（CRC）模型的关系尚不清楚。
探讨冷暴露和辣椒素对 DMH 诱导的 CRC 中 ECM 重塑和 ECM 酶的影响。
对结肠组织切片进行苏木精和伊红、马松三色、苦味酸天狼星红和 Weigert 丽春红染色，观察胶原和弹性蛋白的重塑。此外，通过免疫组织化学法评估 I 型胶原（COL I）、III 型胶原（COL III）、弹性蛋白、基质金属蛋白酶（MMP）1、MMP2、MMP9 和组织特异性基质金属蛋白酶 1（TIMP1）的蛋白表达水平。采用逆转录定量聚合酶链反应（RT-qPCR）法检测大鼠结肠组织中 COL I、COL III、弹性蛋白和赖氨酰氧化酶样-2（LOXL2）的信使 RNA（mRNA）水平。
虽然腺瘤的比例没有差异，但冷暴露和辣椒素组侵袭性肿瘤的比例呈上升趋势。冷暴露组的转移率与其他组相比有所增加。此外，冷暴露和辣椒素组均观察到胶原和弹性蛋白的异常堆积。具体而言，与 DMH 组相比，胶原定量分析显示长度、宽度、角度和直线度增加。与辣椒素组相比，冷暴露组胶原沉积和直线度显著增加。与 DMH 组相比，冷暴露和辣椒素组在结肠组织中 COL I、弹性蛋白和 LOXL2 的蛋白水平及其 mRNA 水平均显著升高，而 COL III 无显著差异。此外，在免疫组织化学评价中，冷暴露和辣椒素组 MMP1、MMP2、MMP9 和 TIMP1 染色增加。
这些结果表明，慢性冷暴露和辣椒素暴露进一步增加了结肠组织中胶原和弹性蛋白的沉积。COL I 和弹性蛋白 mRNA 和蛋白水平的增加可能是导致冷暴露和辣椒素暴露引起的结肠组织 ECM 重塑和硬度变化的原因。LOXL2 的上调表达以及 MMP/TIMP 激活和失活之间的生理失衡可能有助于冷暴露和辣椒素暴露引起的 CRC 的进展。
