Inhibition of Cholesterol Biosynthesis Modulates Epithelial-Mesenchymal Transition in Primary Cicatricial Alopecia Through TGFβ and Angiotensin Receptors
Authors
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Department of Zoology, University of Kerala, Thiruvananthapuram - 695581, Kerala ,IN
Leemon Nikhila -
Department of Zoology, University of Kerala, Thiruvananthapuram - 695581, Kerala ,INSuresh Surya
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Department of Zoology, University of Kerala, Thiruvananthapuram - 695581, Kerala ,INShahul Hameed Najeeb
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Department of Zoology, University of Kerala, Thiruvananthapuram - 695581, Kerala ,INThankachan Mangalathettu Binumon
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Department of Zoology, University of Kerala, Thiruvananthapuram - 695581, Kerala ,INParameswara Panicker Sreejith
DOI:
https://doi.org/10.18311/jer/2023/33509Keywords:
Cholesterol, Fibrosis, Hair, PPARγ, Pioglitazone, TransfectionAbstract
Introduction: Primary Cicatricial Alopecia (PCA) is an autoimmune condition that affects the skin and causes hair loss in patients. In PCA the hair follicles of the patients are irreversibly damaged and replaced with fibrous tissue. This diseased condition lends relevance to our work since the fibrosis raises the potential that PCA may be affected in some way by the Epithelial Mesenchymal Transition (EMT). We used small interfering RNAs (siRNA) of TGFβ, AGTR and their regulators to identify the EMT modulation. Because these molecules mediate the induction of EMT. This study explores the idea of lowering PCA fibrosis by modifying EMT markers. Methods: We chose 7 DHC and BM15766 to investigate the function of cholesterol biosynthesis inhibition. We employed the HFORS in vitro and the mouse in vivo model system to examine EMT regulation PCA. Quantitative real-time PCR was utilised to examine the expression of genes in PCA scalp samples, compound-treated HFORS, and mouse tissues; immunohistochemistry was used to confirm the protein estimate in the scalp samples; and small interfering RNA (siRNA) transfection was used to identify the functional analysis of TGFβ and AGTR. Results: Reduced cholesterol production in PCA patients leads to permanent hair follicle damage. The in vitro and in vivo study using 7DHC and BM15766 revealed cells were positive for the EMT markers. PPARγ, AhR, and AGTR together can act as vital EMT regulators. As a result, the PPARγ agonist, AhR, and AGTR antagonist significantly downregulate the expression of CDH1, SNAIL1, and SMA. The markers of EMT are likewise deregulated by the transfection of siRNA for TGFβ and AGTR. Conclusion: We clarify how EMT is regulated in hair loss circumstances by suppressing cholesterol biosynthesis. We further confirm that EMT modulators (PPARγ, AhR, AGTR, and TGFβ) and siRNA can be employed as potentially effective strategies to slow the advancement of EMT. As a result, we propose these cholesterol and EMT modulators as potential inhibitors in PCA etiology.
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