ROLE OF PHENERGAN IN ABNORMAL SCARS AND KELOIDS

2004 ◽  
Vol 12 (04) ◽  
pp. 471-482
Author(s):  
J. VENUGOPAL ◽  
V. JAYARAMAN ◽  
MARY BABU ◽  
S. RAMAKRISHNA
Keyword(s):  
Dna Synthesis ◽  
Hypertrophic Scar ◽  
Skin Fibroblast ◽  
Collagen Synthesis ◽  
Normal Skin ◽  
Compression Therapy ◽  
Matrix Proteins ◽  
Intralesional Corticosteroid ◽  
Normal Skin Fibroblast

Hypertrophic scar and keloids have affected patients and frustrated physicians for centuries. Hypertrophic scar (HSc) and keloids are a major problem for patients who survive extensive thermal and traumatic skin injuries. HSc and other fibroproliferative disorders are associated with excessive accumulation of collagen and extracellular matrix proteins due to an imbalance between synthesis and degradation. The therapeutic management of hypertrophic scars and keloids include occlusive dressings, compression therapy, intralesional corticosteroid injections, cryosurgery, excision, radiation therapy, laser therapy, interferon therapy and other promising lesser known therapies directed at collagen synthesis. In this study we investigated the effect of phenergan (promethazine hydrochloride) as one of the most potent histamine antagonists on cell proliferation, DNA synthesis and collagen production in fibroblast isolated from human post burn hypertrophic scar, keloids and normal skin. The proliferation of normal skin fibroblast was slightly decreased but hypertrophic scar and keloids showed significant (p<0.001) level of decrease after 72 hours of phenergan (750 μM) treatment. The results of DNA synthesis also significantly (p<0.001) decreased in hypertrophic scar and keloid fibroblasts. Phenergan (1.5 mM) decreased the collagen synthesis upto 61% and 66% in HSc and keloids in comparison to normal skin fibroblast, which showed reduction of 38% after 72 hours. Improved understanding of such regulatory mechanisms may eventually be of therapeutic significance in the control of hypertrophic scar and keloids.

Overexpression of miR-340-5p Inhibits Skin Fibroblast Proliferation by Targeting Kruppel-like Factor 2

2019 ◽  
Vol 20 (13) ◽  
pp. 1147-1154 ◽  
Author(s):  
Ling Chen ◽  
Qian Li ◽  
Xun Lu ◽  
Xiaohua Dong ◽  
Jingyun Li
Keyword(s):  
Gene Ontology ◽  
Skin Fibroblast ◽  
Kegg Pathway ◽  
Normal Skin ◽  
Skin Fibroblasts ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Fibroblast Proliferation ◽  
Pathway Analyses ◽  
Normal Skin Fibroblast

<P>Objective: MicroRNA (miR)-340-5p has been identified to play a key role in several cancers. However, the function of miR-340-5p in skin fibroblasts remains largely unknown. </P><P> Methods: Gain of function experiments were performed by infecting normal skin fibroblast cells with a lentivirus carrying 22-bp miR-340-5p. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) assay. To uncover the mechanisms, mRNA-seq was used. Differentially expressed mRNAs were further determined by Gene Ontology and KEGG pathway analyses. The protein levels were analysed by Western blotting. A dual-luciferase reporter assay was used to detect the direct binding of miR-340-5p with the 3&#039;UTR of Kruppel-like factor 2 (KLF2). </P><P> Results: MiR-340-5p lentivirus infection suppressed normal skin fibroblast proliferation. The mRNAseq data revealed that 41 mRNAs were differentially expressed, including 22 upregulated and 19 downregulated transcripts in the miR-340-5p overexpression group compared with those in the control group. Gene Ontology and KEGG pathway analyses revealed that miR-340-5p overexpression correlated with the macromolecule biosynthetic process, cellular macromolecule biosynthetic process, membrane, and MAPK signalling pathway. Bioinformatics analysis and luciferase reporter assays showed that miR-340-5p binds to the 3&#039;UTR of KLF2. Forced expression of miR-340-5p decreased the expression of KLF2 in normal skin fibroblasts. Overexpression of KLF2 restored skin fibroblast proliferation in the miR-340-5p overexpression group. </P><P> Conclusion: This study demonstrates that miR-340-5p may suppress skin fibroblast proliferation, possibly through targeting KLF2. These findings could help us understand the function of miR-340-5p in skin fibroblasts. miR-340-5p could be a therapeutic target for preventing scarring.</P>

Abstract 15916: Role of Small-cajal Body Associated RNAs (scaRNAs) in Regulation of Cardiomyogenesis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Shivaani Kirankumar ◽  
VINOTH SIGAMANI ◽  
Sheeja Rajasingh ◽  
Jayavardini Vasanthan ◽  
Narasimman Gurusamy ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Heart Defects ◽  
Genetic Disorder ◽  
Normal Skin ◽  
Critical Role ◽  
Cajal Body ◽  
Qrt Pcr ◽  
Induced Pluripotent ◽  
Normal Skin Fibroblast

Introduction: The requirement of non-coding RNAs particularly scaRNAs are playing a critical role in alternative splicing and maturation of mRNAs. Dysregulated splicing of mRNAs has been shown to cause heart defects. In this study, we are comparing the role of scaRNAs during differentiation of induced pluripotent stem cells (iPSCs) into cardiomyocytes (iCMCs) from normal individual and Noonan syndrome (NS) patient. We have selected NS patient cells because it is an autosomal dominant genetic disorder which leads to cardiomyopathy and congenital heart defects in humans. Hypothesis: We hypothesize that scaRNA1 and scaRNA20 have a significant role in the development of cardiomyocytes, and these scaRNAs are dysfunctional in iCMCs derived from NS. Methods and Results: We have compared the normal skin fibroblast-derived iPSCs (N-iPSCs) and N-iCMCs with NS patient-derived NS-iPSCs and NS-iCMCs using quantitative RT-PCR, Western blot and immunofluorescence analyses. We also used the knockdown and overexpression of scaRNA1 and scaRNA20 approaches to delineate the importance of these scaRNAs during cardiomyogenesis. Our qRT-PCR data showed a significantly lower expression of scaRNA1 and scaRNA20 (Fig. A) as well as the cardiac-specific genes CTT and GATA4 (Fig. B) in NS-iCMCs when compared to the normal iCMCs. Furthermore, the qRT-PCR data from the scaRNA20 overexpressed N-iCMC showed an increased expression of cardiac-specific genes (Fig. C) when compared to the N-iCMCs. These studies clearly indicate that scaRNA1 and scaRNA20 plays an important role in cardiomyogenesis. Further studies are underway to explore the mechanisms of these scaRNAs in regulation of cardiac genes. Conclusions: Our findings indicate that scaRNA1 and scaRNA20 are involved in mRNA splicing and maturation of cardiac genes. Moreover, these scaRNAs are dysfunctional in NS patient’s iCMCs and targeting these molecules will have a therapeutic potential for a patient with NS.

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