Let-7i-5p Regulation of Cell Morphology and Migration Through Distinct Signaling Pathways in Normal and Pathogenic Urethral Fibroblasts.

Kaile Zhang,Ranxin Yang,Shukui Zhou,Rong Chen,Jun Chen,Qiang Fu,Er Qi,Xiaolan Fang,Ying Wang

doi:10.3389/fbioe.2020.00428

Abstract

microRNAs regulate subcellular functions through distinct molecular mechanisms. In this study, we used normal and pathogenic fibroblasts in pelvic fracture urethral distraction defects (PFUDD) patients. PFUDD is a common disease that could severely affect patients’ life quality, yet little is known about the molecular mechanism associated with pathogenic fibrosis in PFUDD. Our data showed that let-7i-5p performs a multi-functional role in distinct signaling transduction pathways involved in cell morphology and cell migration in both normal and pathogenic fibroblasts. By analyzing the molecular mechanism associated with its functions, we found that let-7i-5p regulates through its direct target genes involved in collagen metabolism, cell proliferation and differentiation, TGF-beta signaling, DNA repair and ubiquitination, gene silencing and oxygen homeostasis. We conclude that let-7i-5p plays an essential role in regulating cell shape and tissue elasticity, cell migration, cell morphology and cytoskeleton, and could serve as a potential target for clinical treatment of urethral stricture patients.

Highlights

Pelvic fracture urethral distraction defects (PFUDD) is a common disease that could severely affects patients’ life quality, largely due to excessive fibrosis and associated urethral stricture (Zhang et al, 2018)
Little is known about the role of let-7i-5p or the related molecular mechanism involved in normal fibroblast growth or fibrosisrelated scar formation
Based on a recent miRNA profiling using pelvic fracture urethral distraction defects (PFUDD) patients’ tissues, we found that let-7i-5p expression was really high in both normal and pathogenic fibroblasts based on miRNA sequencing

Summary

Introduction

Pelvic fracture urethral distraction defects (PFUDD) is a common disease that could severely affects patients’ life quality, largely due to excessive fibrosis and associated urethral stricture (Zhang et al, 2018). The current incidence of PFUDD is noted to be variable, usually between 5 and 25% of pelvic fractures, with a frequency of 0.32–5/100,000 for men and 0.46–7.25/100,000 for women (Alwaal et al, 2015; Barratt et al, 2018; Dixon et al, 2018). Pelvic fractures resulting in PFUDD has mortality rates between 5 and 33% (Barratt et al, 2018). Fibrosis is a key factor responsible for pathologic changes related to urethral stricture (in both primary or recurrent diseases; Zhao et al, 2018). The major interests are in miR-29 and TGF-beta signaling pathway, focusing on their role of molecular

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Discussion

Conclusion