Retinoids in Stellate Cells: Development, Repair, and Regeneration

Abstract

Stellate cells, either hepatic (HSCs) or pancreatic (PSCs), are a type of interstitial cells characterized by their ability to store retinoids in lipid vesicles. In pathological conditions both HSCs and PSCs lose their retinoid content and transform into fibroblast-like cells, contributing to the fibrogenic response. HSCs also participate in other functions including vasoregulation, drug detoxification, immunotolerance, and maintenance of the hepatocyte population. PSCs maintain pancreatic tissue architecture and regulate pancreatic exocrine function. Recently, PSCs have attracted the attention of researchers due to their interactions with pancreatic ductal adenocarcinoma cells. PSCs promote tumour growth and angiogenesis, and their fibrotic activity increases the resistance of pancreatic cancer to chemotherapy and radiation. We are reviewing the current literature concerning the role played by retinoids in the physiology and pathophysiology of the stellate cells, paying attention to their developmental aspects as well as the function of stellate cells in tissue repair and organ regeneration.

Hepatic stellate cells – from past till present: morphology, human markers, human cell lines, behavior in normal and liver pathology

“…Retinoids play a key role in modulating HSCs activation [ 30 , 43 , 110 , 111 ]. After hepatic insult, Ito cells immediately lose their lipid droplets and retinoid deposits.…”

“…After hepatic insult, Ito cells immediately lose their lipid droplets and retinoid deposits. Also, the expression of LRAT and peroxisome proliferator-activated receptor gamma (PPAR γ ) decrease [ 30 , 43 , 110 , 111 ]. It seems that loss of HSCs lipid droplets is the trigger in the development of hepatic disease [ 30 ].…”

Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair

“…Furthermore, these mesothelial precursor cell populations employ a related set of developmental programs to give rise to fibroblasts and smooth muscle cells. For example, WT1 is expressed by EPDCs as well as by coelomic precursors that give rise to HSCs, lung fibroblasts, hepatic smooth muscle cells, and PSCs (Asahina et al, 2011;Carmona, Barrena, & Munoz-Chapuli, 2019;Ijpenberg et al, 2007;Perez-Pomares et al, 2002;Sontake et al, 2018;Takeichi, Nimura, Mori, Nakagami, & Kaneda, 2013Ariza, 2018. In comparison to WT1, TCF21 is expressed in both overlapping as well as distinct subsets of mesothelial precursors that give rise to cardiac fibroblast and lung lipofibroblast populations (Acharya et al, 2012;Braitsch et al, 2012;Braitsch et al, 2013;Kikuchi, Gupta, et al, 2011;Park et al, 2019;Tandon et al, 2013;Vicente-Steijn et al, 2015Kanisicak, 2016.…”

Tissue Nutrient Environments and Their Effect on Regulatory T Cell Biology

“…Another site of Vitamin A metabolism is the liver. Naïve hepatic stellate cells (HSCs) store retinoids, which can account for nearly 50% of all RA in the body, and produce ATRA upon activation in the local environment (80). In addition to ATRA, activated HSCs can produce TGFb, a potent combination for Treg differentiation.…”