Cholesterolgenic Inhibition Causes Permanent Hair Follicle Damage by Activating Fibrosis Via the Angiotensin Receptor
DOI:
https://doi.org/10.18311/jer/2022/30362Keywords:
Aryl hydrocarbon Receptor, Angiotensin II, Primary Cicatricial Alopecia, Autoimmune Disorder, Peroxisome Proliferator-Activated Receptors γ, Transforming Growth Factor βAbstract
Primary Cicatricial Alopecia (PCA) is a type of inflammatory hair loss disorder that resulted in the permanent damage of the pilosebaceous structure due to fibrosis. Various internal and environmental stimuli caused the breakdown of hair follicle cells. Cholesterol is a crucial component in the formation and differentiation of hair follicles and the overall health of the skin. The loss of hair follicle and aberrant cycles were caused by any inhibition or obstruction of the cholesterol biosynthetic pathways. This study suggests that cholesterologenic changes like precursor formation and inhibition in the hair follicle, trigger inflammation, fibrogenic signaling and leading to fibrosis. TGFβ-SMAD pathways related to the fibrogenic process were significantly expressed during the experimental condition. Angiotensin II receptor, AGTR1, showed a profound effect on the hair follicle cells. Real-time PCR analysis and immunohistochemistry of the patient’s scalp biopsies, HHFORS cells, and mice tissue sample revealed that the fibrotic genes were significantly activated after the treatment of BM15766, a cholesterol biosynthesis inhibitor, and 7- DHC, a sterol precursor. Our study confirmed that fibrosis is developed in the late stage of PCA by the dysregulation of cholesterol biosynthesis pathways in the hair follicle cells.
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