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Cholesterolgenic Inhibition Causes Permanent Hair Follicle Damage by Activating Fibrosis Via the Angiotensin Receptor


Affiliations
1 Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India, India
2 Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India ., India
     

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Primary Cicatricial Alopecia (PCA) is a type of inflammatory hair loss disorder resulting 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 skin’s overall health. The loss of hair follicles and aberrant cycles were caused by inhibiting or obstructing the cholesterol biosynthetic pathways. This study suggests that cholesterologenic changes like precursor formation and inhibition in the hair follicle, trigger inflammation, fibrogenic signaling and lead 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 .

Keywords

Aryl hydrocarbon Receptor, Angiotensin II, Primary Cicatricial Alopecia, Autoimmune Disorder, Peroxisome Proliferator-Activated Receptors γ, Transforming Growth Factor β
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  • Cholesterolgenic Inhibition Causes Permanent Hair Follicle Damage by Activating Fibrosis Via the Angiotensin Receptor

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Authors

Shahul Hameed Najeeb
Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India, India
Thankachan Mangalathettu Binumon
Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India ., India
Suresh Surya
Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India ., India
Leemon Nikhila
Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India ., India
Parameswara Panicker Sreejith
Department of Zoology, Advanced Centre for Regenerative Medicine and Stem cell in Cutaneous Research (AcREM-Stem), University of Kerala, Thiruvananthapuram – 695581, Kerala, India ., India

Abstract


Primary Cicatricial Alopecia (PCA) is a type of inflammatory hair loss disorder resulting 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 skin’s overall health. The loss of hair follicles and aberrant cycles were caused by inhibiting or obstructing the cholesterol biosynthetic pathways. This study suggests that cholesterologenic changes like precursor formation and inhibition in the hair follicle, trigger inflammation, fibrogenic signaling and lead 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 .

Keywords


Aryl hydrocarbon Receptor, Angiotensin II, Primary Cicatricial Alopecia, Autoimmune Disorder, Peroxisome Proliferator-Activated Receptors γ, Transforming Growth Factor β

References





DOI: https://doi.org/10.18519/jer%2F2022%2Fv26%2F217297