Recombinant humanized collagen remodels endometrial immune microenvironment of chronic endometritis through macrophage immunomodulation

作者全名："You, Shuang; Zhu, Yun; Li, Hu; He, Fan; Liu, Shuaibin; Yang, Xia; Wang, Li; Zeng, Hui; Dai, Jingcong; Hu, Lina"

作者地址："[You, Shuang; Li, Hu; He, Fan; Liu, Shuaibin; Wang, Li; Zeng, Hui; Dai, Jingcong; Hu, Lina] Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China; [Zhu, Yun] Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China; [He, Fan; Hu, Lina] Minist Educ, Joint Int Res Lab Reprod & Dev, Chongqing 400010, Peoples R China; [Yang, Xia] Shanxi Jinbo Pharmaceut Co Ltd, Taiyuan 030031, Shanxi, Peoples R China; [Hu, Lina] Reprod & Stem Cell Therapy Res Ctr Chongqing, Chongqing 400010, Peoples R China; [Hu, Lina] Chongqing Med Univ, Ctr Collagen Transformat, Chongqing 400010, Peoples R China"

通信作者："Hu, LA (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Obstet & Gynecol, Chongqing 400010, Peoples R China.; Hu, LA (通讯作者)，Minist Educ, Joint Int Res Lab Reprod & Dev, Chongqing 400010, Peoples R China.; Hu, LA (通讯作者)，Reprod & Stem Cell Therapy Res Ctr Chongqing, Chongqing 400010, Peoples R China.; Hu, LA (通讯作者)，Chongqing Med Univ, Ctr Collagen Transformat, Chongqing 400010, Peoples R China."

来源：REGENERATIVE BIOMATERIALS

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000976351500001

JCR分区：Q1

影响因子：5.6

年份：2023

卷号：10

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：chronic endometritis; recombinant humanized collagen; type III collagen; macrophages

摘要："Recently, evidence has suggested that chronic endometritis (CE) is a crucial factor associated with infertility and failure of assisted reproductive techniques, prompting concern in the reproductive field. Studies have shown that persistent infiltered immune cells stimulation result in the disturbance of endometrial immune microenvironment could lead to the infertility of CE patients finally. Conventional treatments are limited because they lack immune regulation, so it is urgent to develop a novel approach to treat CE and promote embryo implantation in patients with CE. Herein, we prepared recombinant humanized type III collagen (rhCol III) with high cell adhesion activity to regulate macrophages and repair the endometrium. In this study, M1 macrophages and M1 macrophages cultured medium and lipopolysaccharide (LPS) co-stimulated inflammatory endometrium stromal cells (ESCs) were established in vitro to mimic CE condition. rhCol III promoted M1 macrophages toward M2 phenotype, improved cell migration, viability and collagen components of inflammatory ESCs. Also, the inflammatory response of inflammatory ESCs was downregulated after rhCol III treatment. Subsequently, LPS was used for CE rat model and a 28-day observation was performed; inflammatory cells' infiltration, endometrium repair, extracellular matrix (ECM) remodeling and pregnancy outcomes were promoted after rhCol III endometrial infusion. In conclusion, rhCol III promoted (i) macrophage polarization toward M2 macrophages, (ii) pro-inflammatory cytokine production and anti-inflammatory cytokine reduction, (iii) ECM remodeling and (iv) fertility restoration. Meanwhile, rhCol III enhanced cell biological functions by interacting with discoidin domain receptors, regulated cell metabolism and reduced the inflammatory response through the inhibition of the NF-kappa B/YAP signaling pathway. Overall, the results illustrated the potential therapeutic prospects of rhCol III for CE treatment."

基金机构："Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJCXZD2020017]; Shanxi Jinbo Bio-Pharmaceutical Co., Ltd."

基金资助正文："Acknowledgments This work was supported by Scientific and Technological Research Program of Chongqing Municipal Education Commission (Grant No. KJCXZD2020017). We gratefully thank Shanxi Jinbo Bio-Pharmaceutical Co., Ltd., for their assistance in providing rhCol III as designed. Conflicts of interest statement. The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article."