1. Towards Dissecting the Pathogenesis of Retinoid-Induced Hair Loss: All-Trans Retinoic Acid Induces Premature Hair Follicle Regression (Catagen) by Upregulation of Transforming Growth Factor-β2 in the Dermal Papilla 
Kerstin Foitzik, Tanja Spexard, Motonobu Nakamura, Ursula Halsner, Ralf Paus 
Journal of Investigative Dermatology 
Volume 124, Issue 6, Pages (June 2005)
DOI: /j X x
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

2. Figure 1
Human hair follicles after 6 d of organ culture. (A–F) Macroscopic, (a–f) H&E staining. (A+a) Control (anagen VI), (B+b) all-trans retinoic acid (ATRA) 10−10 M (early catagen), arrow: volume of the hair matrix compartment has diminished, (C+c) ATRA 10−8 M (mid-catagen), (D+d) ATRA 10−6 M (late catagen), (E+e) transforming growth factor (TGF)-β2 10 ng per mL (late catagen), (F+f) ATRA 10−8 supplemented with anti-TGF-β1–3, antibody (anti-TGF-β) (anagen VI). M Star: condensed dermal papilla, (arrow, c, d) pigmented lower end of the hair shaft has moved upwards, (c) cessation of pigmentation, arrowhead: epithelial strand in late catagen
Journal of Investigative Dermatology  , DOI: ( /j X x)
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

3. Figure 2
Hair growth and hair cycle slopes after treatment with ATRA and TGF-β2. (A) Graph shows length of hair shafts of all-trans retinoic acid (10−6, 10−8 M) and transforming growth factor (TGF)-β2-treated hair follicles (HF) compared with control (n=30 HF per group) at days 0, 2, 4, and 6 in culture. Statistical significance was calculated using the Mann–Whitney U test. *p<0.05, **p< (B) Corresponding hair-cycle score (HCS). Calculation of the HCS: all HF of each group were staged and each stage of the hair cycle has been scored as follows: anagen=100, early catagen=200, late catagen=300. The HCS indicates the mean of the stages of all HF per group. *p<0.01
Journal of Investigative Dermatology  , DOI: ( /j X x)
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

4. Figure 3
Total number of Ki67- and TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells after 6 d in culture. All-trans retinoic acid-treated hair follicles show an upregulation of apoptotic cells, whereas proliferation is significantly reduced. Statistical significance was calculated using the Mann–Whitney U test. **p<0.01
Journal of Investigative Dermatology  , DOI: ( /j X x)
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

5. Figure 4
Down regulation of proliferation and upregulation of TGF-β2 hair scripts in the dermol papilla after ATRA treatment. (A) Left panel: Human anagen VI hair follicle (HF) after 6 d in culture. Red fluorescence shows Ki67-positive cells and green fluorescence labels TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells (arrows). Right panel: all-trans retinoic acid (ATRA) 10−8 M treated anagen VI HF after 6 d in culture. Ki67-positive cells in the hair bulb are downregulated. TUNEL-positive cells (arrows) increased compared with control. (B) Transforming growth factor (TGF)-β2 (green) expression in human HF after 4 d in culture without and with ATRA treatment. Left: control; right: ATRA 10−8 M treated anagen HF. Note TGF-β2 upregulation in the dermal papilla of ATRA-treated HF. Lower pictures show magnification of upper dermal papilla sections. IRS, inner root sheath; ORS, outer root sheath; DP, dermal papilla
Journal of Investigative Dermatology  , DOI: ( /j X x)
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions

6. Figure 5
Transforming growth factor (TGF)-β2 light-cycler RT-PCR. RNA was separately extracted from the distal part (hair shaft) and the proximal part including dermal papilla (hair bulb) of each hair follicle (HF). Upper graph shows GAPDH and lower graph shows TGF-β2 relative mRNA expression. ***p<0.0006
Journal of Investigative Dermatology  , DOI: ( /j X x)
Copyright © 2005 The Society for Investigative Dermatology, Inc Terms and Conditions