MiR‐10a and miR‐181c regulate collagen type I generation in hypertrophic scars by targeting PAI‐1 and uPA

Abstract

Edited by Tamas DalmayKeywords: MicroRNA Hypertrophic scar Collagen type 1 Urokinase type plasminogen activator Plasminogen activator inhibitor-1 a b s t r a c t Urokinase type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been proposed to play key roles in extracellular matrix (ECM) deposition in hypertrophic scars (HS). Here, we found that in HS fibroblasts (HFs) miR-181c and miR-10a were differentiallyexpressed and targeted uPA and PAI-1, respectively. The production of Type 1 collagen (Col1) was inhibited by miR-181c knockdown or miR-10a overexpression in HFs, and this resulted in increased levels of metalloproteinase 1 (MMP1). These results suggest that the miR-181c-uPA and miR-10a-PAI-1 regulatory pathways have an integral role in HS pathogenesis.

The Urokinase Receptor-Derived Peptide UPARANT Mitigates Angiogenesis in a Mouse Model of Laser-Induced Choroidal Neovascularization

“…In fact, several microRNAs have been demonstrated to regulate uPA expression in humans. 51,52 Upregulation of uPA/uPAR in CNV could be explained by presupposing that RPE and choroidal endothelial cells, both known to express uPA and uPAR, 13,14 may release soluble factors in response to the laser injury. Such factors could then exert activity in a paracrine fashion and increase the expression of uPA and uPAR, in turn representing the switch to induce choroidal angiogenesis.…”

Non-Coding RNAs: New Players in Skin Wound Healing

“…88 Further miRNAs involved in pathological scar formation include miR-21, which promotes fibroblast proliferation in HTS formation and in keloids; miR-200b and miR-199a-5p, which inhibit fibroblast proliferation; and miR-10a and -181c, which regulate collagen I generation (Table 3). 89–95 …”

Overexpression of SerpinE2/protease nexin-1 Contribute to Pathological Cardiac Fibrosis via increasing Collagen Deposition

“…Since uPA-PN-1 forms a complex with uPAR (uPA-uPAR-PN-1)33, which then binds to the cells and are rapidly internalized and degraded by the low density lipoprotein-related receptor protein (LRP)5. uPA play an important role in promoting extracellular matrix (ECM) deposition34. Intriguingly, serpinE2 requires to internalize uPAR-bound uPA to form the complex, then further inhibits the uPA that plays a pivotal role by mediating the degradation of extracellular matrix proteins35.…”

“…8). uPA/uPAR system plays crucial roles in ECM deposition34, which is associated with myocardial fibrosis and remodeling42.…”