PMID- 34868320 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211207 IS - 1687-966X (Print) IS - 1687-9678 (Electronic) VI - 2021 DP - 2021 TI - Dual Effects of Hypoxia-Inducible Factors-1 Alpha in Bleomycin-Induced Pulmonary Fibrosis Treated by Human Umbilical Cord Mesenchymal Stem Cells. PG - 6658855 LID - 10.1155/2021/6658855 [doi] LID - 6658855 AB - Pulmonary fibrosis (PF) is a kind of lung disease characterized by scar formation and inflammation damage. Mesenchymal stem cells (MSCs) are considered a promising therapy because of multidirectional differentiation and immune regulation. Our research was designed for identifying the preventative defensive ability and therapeutic effect of human umbilical cord mesenchymal stem cells (HUCMSCs). HUCMSCs were administered before or after bleomycin injection in different groups of C57BL/6 mice. We calculated the survival time of mice, the lung coefficients, contents of hydroxyproline, and pathological scores. The expression levels of HIF-1alpha (hypoxia-inducible factor-1alpha), alpha-SMA (alpha-smooth muscle actin), gammaH(2)AFX (gammaH2A histone family, member X), ZO-1 (zonula occludens-1), ROS (reactive oxygen species) content, and proliferation ability of A549 cells were detected after treatment with bleomycin and HUCMSCs conditioned medium (HUCMSCs-CM), respectively, or together in vitro. In addition, we examined the secretome of HUCMSCs in regular and inflammatory stimulation conditions. Our results demonstrated that prophylactic HUCMSC administration before bleomycin-induced modeling process could significantly meliorate damage to pulmonary fibrosis. After the deletion of HIF-1alpha, damage markers in A549 cells were significantly reduced in therapeutic administration condition. However, it was the opposite in prophylactic administration condition. The results confirmed that HUCMSCs had available preventive effect on bleomycin-induced pulmonary fibrosis in vivo and in vitro. However, it may have a negative effect in therapeutic administration condition because of the dual effect of HIF-1alpha. CI - Copyright (c) 2021 Hongpeng Zhang et al. FAU - Zhang, Hongpeng AU - Zhang H AD - Asia Stem Cell Regenerative Pharmaceutical Co. Ltd., 2066 Wangyuan Road, Shanghai 201499, China. FAU - Wang, Hao AU - Wang H AD - Asia Stem Cell Regenerative Pharmaceutical Co. Ltd., 2066 Wangyuan Road, Shanghai 201499, China. FAU - Xia, Yong AU - Xia Y AD - Asia Stem Cell Regenerative Pharmaceutical Co. Ltd., 2066 Wangyuan Road, Shanghai 201499, China. FAU - Qi, Nianmin AU - Qi N AUID- ORCID: 0000-0002-8580-0925 AD - Asia Stem Cell Regenerative Pharmaceutical Co. Ltd., 2066 Wangyuan Road, Shanghai 201499, China. LA - eng PT - Journal Article DEP - 20211126 PL - United States TA - Stem Cells Int JT - Stem cells international JID - 101535822 PMC - PMC8642016 COIS- The authors indicated no potential conflicts of interest. EDAT- 2021/12/07 06:00 MHDA- 2021/12/07 06:01 PMCR- 2021/11/26 CRDT- 2021/12/06 09:09 PHST- 2020/12/25 00:00 [received] PHST- 2021/11/01 00:00 [revised] PHST- 2021/11/13 00:00 [accepted] PHST- 2021/12/06 09:09 [entrez] PHST- 2021/12/07 06:00 [pubmed] PHST- 2021/12/07 06:01 [medline] PHST- 2021/11/26 00:00 [pmc-release] AID - 10.1155/2021/6658855 [doi] PST - epublish SO - Stem Cells Int. 2021 Nov 26;2021:6658855. doi: 10.1155/2021/6658855. eCollection 2021.