Inhibition of MicroRNA‐21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis

Jafarinejad-Farsangi, Saeideh; Farazmand, Ali; Gharibdoost, Farhad; Karimizadeh, Elham; Noorbakhsh, Farshid; Faridani, Habibeh; Mahmoudi, Mahdi; Jamshidi, Ahmad Reza

doi:10.1111/ijd.13308

Cited by 34 publications

(22 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies have focused on the role of epigenetics such as miRNAs in skin-involved autoimmune diseases specially SSc. 41,42 Furthermore, dysregulated survivin-targeting miRNAs have provided new perspectives in the field of cancer. 23 Therefore, much more needs to be learned about the regulatory role of survivin-targeting miRNAs in SSc.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression

Manesh

Farazmand

Gharibdoost

et al. 2019

IJAAI

Self Cite

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is characterized by excessive production of collagens by fibroblasts that leads to vast fibrosis. Resistance to apoptosis is one of the possible underlying mechanisms of fibrosis in these patients. Survivinis involved in inhibition of apoptosis and aberrantly functions in SSc. Since dysregulation of survivin-targeting microRNAs (miRNAs) has frequently been observed in cancer and some autoimmune disorders, this study aimed to investigate their expression status in dermal fibroblasts from SSc patients. DiffuseSSc patients were selected according to American College of Rheumatology criteria. Isolated fibroblasts from 10 SSc and 10 healthy skin biopsies were cultured. After examining purity of the cells, mRNA and miRNAs extraction was performed followed by complementary DNA (cDNA) synthesis. Relative expressions ofsurvivin mRNA, miR-16-5p, miR-320a, miR-218-5p, miR-708-5p and miR-542-3p were analyzed using real time PCR. Survivin mRNA expression was significantly 1.85-fold upregulated in fibroblasts from SSc patients compared with healthy controls (p=0.046). Among the studied miRNAs, miR-542-3p expression was significantly decreased (p=0.033), while enhanced expression of miR-708-5p was observed in SSc fibroblasts (p=0.05) in comparison to healthy subjects. Downregulation of miR-542-3p significantly correlated with survivin overexpression (r=˗0.45, p=0.049). Downregulation of miR-542-3p that is correlated with higher surviving expression levels might be a possible cause of apoptosis resistance in SSc fibroblasts, hence providing a new understanding of the disease pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression

Manesh

Farazmand

Gharibdoost

et al. 2019

IJAAI

Self Cite

View full text Add to dashboard Cite

show abstract

“…To date, the powerful gene regulators microRNAs have been implicated in many pathophysiological processes, including cell development, proliferation, apoptosis, and carcinogenesis [20,38,39]. Accumulating evidence has shown that many miRNAs are also critically involved in the pathogenesis of human tissue fibrosis of in several organs [40].…”

Section: Discussionmentioning

confidence: 99%

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor

Shi

Liu

et al. 2018

Cell Cycle

View full text Add to dashboard Cite

Systemic sclerosis (SSc) is a multisystemic fibrotic disease characterized by excessive collagen deposition and extracellular matrix synthesis. Though transforming growth factor-β (TGF-β) plays a fundamental role in the pathogenesis of SSc, the mechanism by which TGF-β signaling acts in SSc remains largely unclear. Here, we showed that TGF-β type II receptor (TGFBR2) was significantly upregulated in both human SSc dermal tissues and primary fibroblasts. In fibroblasts, siRNA-induced knockdown of TGFBR2 resulted in a reduction of p-SMAD2/3 levels and reduced production of type I collagen. Additionally, functional experiments revealed that downregulation of TGFBR2 yielded an anti-growth effect on fibroblasts through inhibiting cell cycle progression. Further studies showed that miR-3606-3p could directly target the 3'-UTR of TGFBR2 and significantly decrease the levels of both TGFBR2 mRNA and protein. Furthermore, SSc dermal tissues and primary fibroblasts contain significantly reduced amounts of miR-3606-3p, and the overexpression of miR-3606-3p in fibroblasts replicates the phenotype of TGFBR2 downregulation. Collectively, our findings demonstrated that increased TGFBR2 could be responsible for the hyperactive TGF-β signaling observed in SSc. Moreover, we identified a pivotal role for miR-3606-3p in SSc, which acts, at least partly, through the attenuation of TGF-β signaling via TGFBR2 repression, suggesting that the regulation of miR-3606-3p/TGFBR2 could be a promising therapeutic target that could improve the treatment strategy for fibrosis.

show abstract

“…Bcl-2 Inhibition of miR-21 expression induced apoptosis in SSc fibroblasts [24] Melanoma SPRY1, PDCD4 and PTEN Affects the proliferation, migration, and apoptosis of human melanoma A375 cells [25] miR-29…”

Section: Ptenmentioning

confidence: 99%

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes

et al. 2020

View full text Add to dashboard Cite

In the past decades, the key roles of most microRNA in dermatosis and skin development have been explored one after another. Among them, microRNA-31 (miR-31) has a prominent role in the regulation of keratinocytes. Numerous studies show that miR-31 can positively regulate the proliferation, differentiation and cell activity of keratinocytes via regulating the NF-κB, RAS/MAPK, Notch signaling pathways, and some cytokines. At present, the interaction between miR-31 and the NF-κB signaling pathway in keratinocytes is a hot research topic. The positive feedback loop formed by miR-31 and NF-κB signaling may bring new ideas for the prevention of psoriasis. The abnormal state of keratinocytes is usually the pathological basis of many skin and immune system diseases. Therefore, strengthening the ability to regulate keratinocytes may be a breakthrough for a variety of diseases. At the same time, miR-31's capacity to accelerate wound healing via positively regulating keratinocytes should be further investigated in the treatment of chronic ulcers and trauma.

show abstract

Inhibition of MicroRNA‐21 induces apoptosis in dermal fibroblasts of patients with systemic sclerosis

Abstract: Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR-21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.

Cited by 34 publications

References 58 publications

Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression

Downregulation of miR-542-3p Contributes to Apoptosis Resistance in Dermal Fibroblasts from Systemic Sclerosis Patients via Survivin Overexpression

MiR-3606-3p inhibits systemic sclerosis through targeting TGF-β type II receptor

MicroRNA-31 Can Positively Regulate the Proliferation, Differentiation and Migration of Keratinocytes

Contact Info

Product

Resources

About