Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study / 医学前沿

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10

Fenugreek (Trigonella foenum-graceum) increases postmenopausal fibroblast-associated COL1A1 and COL3A1 production dominantly through its binding to estrogen receptor beta

In postmenopausal women, oral or topical administration of estradiol increases skin thickness and collagen synthesis,such as collagen type 1 alpha 1 (COL1A1) and collagen type 3 alpha 1 (COL3A1). Due to undesirable side effectsof estradiol, such as risks of breast and endometrium pathology, topical phytoestrogens are alternative treatments foraging-related skin changes. Phytoestrogen is a nonsteroidal substance derived from plants, like fenugreek (Trigonellafoenum-graceum L.), which has an estrogen like composition that appears to mimic estradiol. The mechanism ofaction remains unknown, especially in fibroblast-associated COL1A1 and COL3A1 production. In vitro experimentswere conducted using postmenopausal women's fibroblasts with estrogen receptor (ER) antagonists. Cell isolationused explant and enzymatic techniques with ELISA kit (MyBioSource, California) for COL1A1 and COL3A1. Pairedstudent t-tests compared results between control (no treatment), fenugreek extract 2 µg/ml alone, fenugreek extract 2µg/ml with receptor antagonists for ERα, ERβ, and both receptors. Greater suppresion of COL1A1 and COL3A1 wereshown by both antagonists ERα / ERβ group and antagonist ERβ group compared to antagonist ERα group. Theseresults indicate that the fenugreek increases secretion of COL1A1 and COL3A1 through ERα, ERβ, and is mainlymediated by ERβ in post menopausal women’s fibroblasts.

The Effect of Trigonella foenum-graceum L. (Fenugreek) Towards Collagen Type I Alpha 1 (COL1A1) and Collagen Type III Alpha 1 (COL3A1) on Postmenopausal Woman's Fibroblast

Trigonella foenum-graceum L. (fenugreek) is a phytoestrogen, a nonsteroidal organic chemical compound from plants which has similar mechanism of action to sex hormone estradiol-17β. This study aims to assess the effectivity of fenugreek seeds extract on collagen type I alpha 1 (COL1A1) and collagen type III alpha 1 (COL3A1) which are both decreased in aging skin and become worsen after menopause. This in vitro experimental study used old human dermal fibroblast from leftover tissue of blepharoplasty on a postmenopausal woman (old HDF). As a control of the fenugreek's ability to trigger collagen production, we used fibroblast from preputium (young HDF). Subsequent to fibroblast isolation and culture, toxicity test was conducted on both old and young HDF by measuring cell viability on fenugreek extract with the concentration of 5 mg/mL to 1.2 µg/mL which will be tested on both HDF to examine COL1A1 and COL3A1 using ELISA, compared to no treatment and 5 nM estradiol. Old HDF showed a 4 times slower proliferation compared to young HDF (p<0.05). Toxicity test revealed fenugreek concentration of 0.5 – 2 µg/mL was non-toxic to both old and young HDF. The most significant fenugreek concentration to increase COL1A1 and COL3A1 secretion was 2 µg/mL (p<0.05).

COL3A1 promotes colorectal cancer growth and its potential regulation mechanism / 复旦学报（医学版）

Objective To investigate the effect of COL3A1 on the occurrence and development of colorectal cancer and its potential regulation mechanism.Methods COL3A1 expression was downregulated by small interfering RNA (siRNA) and was up-regulated by transient overexpression.The levels of COL3A1 protein and Akt/mTOR proteins were detected by Western blot.Cell proliferation was detected by MTT assay,cell counting and plate clone formation assay.Results Over expression of COL3A1 increased the proliferation rate of colorectal cancer cells significantly and activated the Akt/mTOR signaling pathway with increasing the expression of downstream genes.The proliferation rate and the flat plate clone formation of colorectal cancer cells were significantly inhibited with COL3A1 silencing.Conclusions COL3A1 played an important role in promoting the growth of colorectal cancer,which suggested that it may be a potential target for clinical detection and treatment of colorectal cancer.

Genetic Analysis of Three Korean Patients with Clinical Features of Ehlers-Danlos Syndrome Type IV

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotidcavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor beta receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.