Oxygen–Glucose Deprivation Promoted Fibroblast Senescence and Collagen Expression via IL11

Abstract

Cell senescence is one of the most important forms of injury induced by cardiovascular and other ischemic diseases. Fibroblasts are important participants in tissue repair after ischemic injury and the main source of IL11 secretion. However, the roles of oxygen–glucose deprivation (OGD) and IL11 in promoting fibroblast senescence and their regulatory mechanisms remain unclear. This study selected the NIH3T3 and L929 fibroblast cell lines as research objects. We found that OGD could induce the expression of p53, P16, p21, and collagen in fibroblasts. In the condition of OGD, when IL11 intervened, fibroblasts’ senescence and collagen expression were changed. Some studies have found that changes in kynurenine (KYN) metabolism are related to aging diseases, and indoleamine 2,3-dioxygenase 1 (IDO1) is a key rate-limiting enzyme in the KYN metabolic pathway. We found that KYN secretion decreased after OGD increased fibroblast senescence, and inhibition of IL11 promoted IDO1 and increased KYN secretion. These results suggest that OGD may promote fibroblast senescence and collagen expression via IL11 inhibition of the IDO1/KYN metabolic pathway. Therefore, the revealed mechanism of OGD-promoted fibroblast senescence could provide an effective theoretical basis for the clinical treatment of aging-related ischemic diseases.

The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence

“…Briefly speaking, tissue protein extraction and Western blotting were carried out as described [38]. Protein mixtures were normalized to 20 µg and loaded into each well and separated using 10-15% sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis.…”

High-Intensity Focused Ultrasound Increases Collagen and Elastin Fiber Synthesis by Modulating Caveolin-1 in Aging Skin

“…Studies indicate that Cav-1 plays a key role in cellular senescence [ 7 , 8 ]. Senescent dermal fibroblasts exhibit increased expression of Cav-1 and several senescence markers, including p21, p16, and p53, accompanied by a decreased capacity for collagen synthesis [ 9 , 10 , 11 ]. Moreover, in aging skin from mice and humans, reduced collagen type I levels are accompanied by Cav-1 upregulation [ 12 ].…”

“…Studies indicate that Cav-1 plays a key role in cellular senescence [7,8]. Senescent dermal fibroblasts exhibit increased expression of Cav-1 and several senescence markers, including p21, p16, and p53, accompanied by a decreased capacity for collagen synthesis [9][10][11]. Moreover, in Despite the link between HIFU and collagen synthesis and the potential for heat to modulate Cav-1 expression, whether HIFU modulates Cav-1 expression directly to promote increased collagen synthesis in the skin remains unknown.…”