Isotretinoin is indirectly effective in sebocytes

Self Cite

Current experimental research on acne pathophysiology has revealed a more complicated background than the classically reported four-factor aetiology. Cells of the pilosebaceous unit, which represent the template for the development of acne lesions, seem to be parallelly affected by endocrinological/metabolic factors as well as inflammatory/immunological ones that cooperate in sebocyte differentiation and lipogenesis. Indeed, the unique programme of sebocyte terminal differentiation and death, the so called holocrine secretion, is influenced by inflammatory and metabolic (lipid) signalling with common denominator the selective regulation of peroxisome proliferator-activated receptors. Autophagy provides substrates for energy generation and biosynthesis of new cell structure proteins contributing to the normally increased sebaceous gland metabolic functions, which are also regulated by extracellular calcium signalling, essential lipids and hormones. The ultimate differentiation product of human sebocytes, sebum, co-regulates the inflammatory sebocyte status. Sebum composition is controlled among others by Propionibacterium acnes and other bacteria, sexual hormones, neuropeptides, endogenous opioids and environmental agents, which may function as endocrine disruptors. Diet may also be an important source of substrates for the synthesis of pro-inflammatory and anti-inflammatory sebaceous lipids. Sebum changes might induce inflammation and initiate underlying immune mechanisms leading to acne lesions. Current new therapeutic efforts on acne concentrate on anti-inflammatory/immunologically active concepts, which are able to regulate sebaceous lipogenesis. At last, current molecular studies based on published molecular data sets confirmed the major role of inflammation in acne development.

Section: New Aspects Of Acne Treatmentmentioning

confidence: 99%

Endocrinology and immunology of acne: Two sides of the same coin

Zouboulis

2020

Self Cite

“…This is demonstrated, for instance, by recent scholarly reviews on SG physiology, [2] endocrinology and immunology, [3] neurobiology, [4] its roles in acne [4,5] and beyond acne [6] and original works on different areas of SG function, including fascinating research on sebaceous lipogenesis. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] Such a development was unthinkable in the 1960s, when the American master of dermatology, Prof. Albert M.…”

Section: The Fir S T S Tepsmentioning

confidence: 99%

“…This is demonstrated, for instance, by recent scholarly reviews on SG physiology, [ 2 ] endocrinology and immunology, [ 3 ] neurobiology, [ 4 ] its roles in acne [ 4,5 ] and beyond acne [ 6 ] and original works on different areas of SG function, including fascinating research on sebaceous lipogenesis. [ 7–22 ] Such a development was unthinkable in the 1960s, when the American master of dermatology, Prof. Albert M. Kligman, has shocked the scientific word with his aphorism “The SG is… a living fossil with a past but not future.”. [ 23 ] This provocative and unsurpassable statement seemed to seal the future of SG research.…”

Section: The First Stepsmentioning

confidence: 99%

Sebaceous gland: Milestones of 30‐year modelling research dedicated to the “brain of the skin”

Zouboulis

Yoshida

et al. 2020

Self Cite

“…In this model, a central role of 4,5‐bisphosphosphate 3‐kinase catalytic subunit gamma gene (PI3KCG) and its related pathway, including p53 and IGF1, has been reported. [ 50 ] Moreover, isotretinoin activated the PI3KCG/Akt/FoxO pathway not only in SZ95 sebocytes in vitro but also in sebaceous glands of isotretinoin‐treated patients with acne. [ 51 ]…”

Section: Hypothesis: Altered Cell Differentiation Is Linked To Dysregmentioning

confidence: 99%

Acne as an altered dermato‐endocrine response problem

Briganti

Flori

Mastrofrancesco

et al. 2020

Acne is the most common skin disease in adolescent Westernized populations. Several data support the involvement of the mammalian target of rapamycin complex 1 (mTORC1) signalling in the interplay between androgens, insulin, insulin-like growth factor (IGF1) and high-glycaemic index diet in acne. The peroxisome proliferator-activated receptor γ (PPARγ) is involved in both differentiation and anti-inflammatory response. Low differentiated sebocytes showed decreased expression of PPARγ and increased level of insulin and IGF-1 receptors, resulting in the production of acne-like sebum and inflammatory mediators. In this viewpoint, we discuss how in acne the dysregulation of proliferation and differentiation processes in sebocytes and keratinocytes may be associated with altered response to androgens and other hormones, such as insulin or IGF-1. Moreover, we propose PPARγ modulation as an innovative therapeutic approach to normalize sebocyte differentiation process, interfering with the different mechanisms involved in altered pilosebaceous unit.