Articles
| Open Access | Immunolocalization and Developmental Expression Profiling of Hepatocyte Growth Factor (HGF), IGF-I, FGF2, and TGF-α in Hepatorenal Tissues of Anser anser Across Hatching and Post-Hatching Ontogeny
Dr. Ayesha Rehman , Department of Veterinary Anatomy and Histology Faculty of Veterinary and Animal Sciences National University of Sciences and Wildlife Research, Lahore, Pakistan Dr. Bilal Ahmed Khan , Department of Wildlife Biology and Pathobiology Institute of Veterinary and Ecological Sciences University of Veterinary and Environmental Studies, Islamabad, PakistanAbstract
The coordinated regulation of growth factors is fundamental to organogenesis, particularly in highly metabolic organs such as the liver and kidney. This study synthesizes developmental immunohistochemical evidence on the spatial and temporal expression patterns of Hepatocyte Growth Factor (HGF), Insulin-like Growth Factor-I (IGF-I), Fibroblast Growth Factor 2 (FGF2), and Transforming Growth Factor-alpha (TGF-α) in the hepatorenal system of Anser anser during hatching and post-hatching ontogeny. Drawing upon comparative avian developmental biology and mammalian embryological frameworks, the research explores how these signaling molecules orchestrate cellular proliferation, differentiation, and tissue remodeling. Prior studies demonstrate that growth factor networks are deeply conserved across vertebrate species and play critical roles in renal and hepatic morphogenesis (Mercola and Stiles, 1988; Matsumoto and Nakamura, 2001). Immunohistochemical localization techniques, as established in avian and mammalian models, reveal dynamic expression shifts during developmental transitions, particularly in nephrogenic and hepatogenic zones. Findings from comparative literature indicate that HGF and FGF signaling pathways are crucial regulators of epithelial–mesenchymal interactions, while IGF-I modulates proliferative expansion and metabolic maturation. TGF-α further contributes to epithelial growth regulation and tissue differentiation balance. The integration of these signaling pathways suggests a tightly coordinated developmental network governing hepatorenal maturation in geese. This study highlights gaps in species-specific molecular mapping in Anser anser and emphasizes the need for high-resolution temporal profiling to better understand avian developmental physiology.
Keywords
Immunolocalization, Hepatocyte Growth Factor, IGF-I, FGF2
References
Abood DA, Reshag AF, Azhar SK, and Aziz M (2014). Comparative anatomical and histological features of the kidney in Harrier (Circus aueroginosus), chicken (Gallus domesticus) and Mallard duck (Anas platyrhynchos). The Iraqi Journal of Veterinary Medicine, 38(1): 107-113.
Ahmad Alabdallah Z, Norezzine A, Anatolyevich Vatnikov Y, Alekseevich Nikishov A, Vladimirovich Kulikov E, Ravilievna Gurina R, Alexandrovna Krotova E, Il'yasovna Khairova N, Ivanovna Semenova V, Valerievna Magdeeva T et al. (2021). Influence of different genders of Japanese Quail on the functional state of kidneys. Archive of Razi Institute, 76(3): 667-680.
Alison MR, Nasim MM, Anilkumar TV, and Sarraf CE (1993). Transforming growth factor-α immunoreactivity in a variety of epithelial tissues. Cell Proliferation, 26(5): 449-460.
Aslan Ş (2018). Üriner sistem, In: Ş. Aslan (Editor), Kanatlı histolojisi [Poultry histology], Baskı, Dora Yayınevi, Bursa, pp. 85-99. Available at: https://dorayayincilik.com.tr/kitap-kanatli-histolojisi--439.html
Beenken A and Mohammadi M (2009). The FGF family: Biology, pathophysiology and therapy. Nature Reviews Drug Discovery, 8(3): 235-253.
Bingöl SA, Deprem T, İlhan Aksu S, Koral Taşçı S, Ermutlu D, and Aslan Ş (2024). Immunohistochemical localization of leptin and ghrelin in kidney tissue of capsaicin administered diabetic and non-diabetic Rats. Kafkas University Faculty of Veterinary Medicine Journal, 30(3): 341-347.
Bolin G and Burggren WW (2013). Metanephric kidney development in the chicken embryo: Glomerular numbers, characteristics and perfusion. Comparative Biochemistry and Physiology, 166(2): 343-350.
Burgess AW (1989). Epidermal growth factor and transforming growth factor α. British Medical Bulletin, 45(2): 401-424.
Cancilla B, Ford-Perriss MD, and Bertram JF (1999). Expression and localization of fibroblast growth factors and fibroblast growth factor receptors in the developing rat kidney. Kidney International, 56(6): 2025-2039.
Carev D, Saraga M, and Saraga-Babic M (2008). Expression of intermediate filaments, EGF and TGF-α in early human kidney development. Journal of Molecular Histology, 39(2): 227-235.
Carlson MB (2018). Human embryology and developmental biology, 6th Edition, Elsevier Health Science., USA, pp. 318-340, 358-372. Available at: https://books.google.com.tr/books?hl=tr&lr=&id=iyx6DwAAQBAJ&oi=fnd&pg=PP1&dq=human+embryology+carlson+2018&ots=ZDjAF_qX08&sig=_wLtGXaYQVFvddeFp8lC7W7LlU8&redir_esc=y#v=onepage&q=human%20embryology%20carlson%202018&f=false
Choi JW, Kim SW, Kim HS, Kang MJ, Kim SA, Han JY, Kim H, and Ku SY (2024). Effects of melatonin, GM-CSF, IGF-1, and LIF in culture media on embryonic development: Potential benefits of individualization. International Journal of Molecular Sciences, 25(2): 751.
Coppola D, Ouban A, and Gilbert-Barness E (2009). Expression of the insulin-like growth factor receptor 1 during human embryogenesis. Fetal and Pediatric Pathology, 28(2): 47-54.
Çöllü F and Gürcü B (2017). Development of embryonic chick liver and distribution of eNOS, iNOS, laminin α1. Celal Bayar University Journal of Science, 13(2): 311-318.
Davies J (2001). Intracellular and extracellular regulation of ureteric bud morphogenesis. Journal of Anatomy, 198(Pt 3): 257-264.
Deprem T, Aksu SI, Taşçi SK, Bingöl SA, Gülmez N, and Aslan Ş (2020). Immunohistochemical distributions of HGF and PCNA in the kidneys of diabetic and non-diabetic mice. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 26(3): 321-327.
Defrances MC, Wolf HK, Michalopoulos GK, and Zarnegar R (1992). The presence of hepatocyte growth factor in the developing rat. Development, 116(2): 387-395.
Derynck R (1992). The physiology of transforming growth factor-α. Advances in Cancer Research, 58: 27-52.
Diaz Ruiz C, Asbert M, and Pérez-Tomás R (1996). Immunochemical study of a transforming growth factor-alpha-related protein in the chicken kidney. Kidney International, 49(4): 1053-1063.
Diaz Ruiz C, Perez-Tomas R, Cullere X, and Domingo J (1993). Immunohistochemical localization of transforming growth factor and epidermal growth factor-receptor in the mesonephros and metanephros of the chicken. Cell and Tissue Research, 271(1): 3-8.
Doaa MM, Enas AEH, Hassan AHS, and Fatma A (2013). Histogenesis of liver of Dandarawi chicken. American Journal of Life Science Research, 1(2): 47-58. Available at: https://www.semanticscholar.org/paper/Histogenesis-of-Liver-of-Dandarawi-Chicken-DoaaHassan/f94d9872316bd4735a21976032bee57e498a5b44
Drummond IA, Mukhopadhyay D, and Sukhatme VP (1998). Expression of fetal kidney growth factors in a kidney tumor line: role of FGF2 in kidney development. Experimental Nephrology, 6(6): 522-533.
Erhan F and Ergün L (2018). Comparison of carbohydrate and fat metabolism in bird and mammal liver. Mehmet Akif Ersoy University Journal of Health Sciences Institute, 6(1): 33-42.
Ermutlu and Aslan, 2025
844
Floege J, Eng E, Lindner V, Alpers CE, Young BA, Reidy MA, and Johnson RJ (1992). Rat glomerular mesangial cells synthesize basic fibroblast growth factor. The Journal of Clinical Investigation, 90(6): 2362-2369.
Gonzalez AM, Buscaglia M, Ong M, and Baird A (1990). Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues. The Journal of Cell Biology, 110(3): 753-765.
Gurevich E, Segev Y, and Landau D (2021). Growth hormone and IGF1 actions in kidney development and function. Cells, 10(12): 3371.
Hashemnia S, Shojaei B, and Razavi H (2015). Liver histogenesis in chukar partridge (Alectoris chukar) embryo. Anatomical Science, 12(3): 129-136. Available at: http://anatomyjournal.ir/article-1-117-en.html
Hassa O and Aştı RN (1997). Embriyoloji [Embryology], 3. Baskı, Yorum Basın Yayın, Ankara, pp. 117, 129-133.
Hsu SM, Raine L, and Fanger H (1981). Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society, 29(4): 577-580.
Iida I, Johkura K, Teng R, Kubota S, Cui L, Zhao X, Ogiwara N, Okouchi Y, Asanuma K, Nakayama J et al. (2003). Immunohistochemical localization of hepatocyte growth factor activator (HGFA) in developing mouse liver tissues. The Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society, 51(9): 1139-1149.
Kara H, Özüdoğru Z, Balkaya H, and Özdemir D (2019). Morphologic and histologic observation of Red-Legged Partridge’s (Alectoris chukar) liver. Van Veterinary Journal, 30(3): 159-161.
König HE, Korbel R, and Liebich HG (2016). Avian anatomy textbook and colour atlas, 2nd Edition, pp. 109-110.
Le Roith D (1997). Insulin-like growth factors. New England Journal of Medicine, 336(9): 633-640.
Le Roith D, Bondy C, Yakar S, Liu J, and Butler A (2001). The somatomedin hypothesis. Endocrine Reviews, 22(1): 53-74.
Liu Y (2002). Hepatocyte growth factor and the kidney. Current opinion in Nephrology and Hypertension, 11(1): 23-30.
Makarevich AV and Markkula M (2002). Apoptosis and cell proliferation of bovine embryos stimulated with insulin-like growth factor-I during in vitro maturation and culture. Biology of Reproduction, 66(2): 386-392.
Matsumoto K and Nakamura T (2001). Hepatocyte growth factor: Renotropic role and potential therapeutics for renal diseases. Kidney International, 59(6): 2023-2038.
McGeady TA, Quinn PJ, Fitzpatrick ES, and Ryan MT (2006). Veterinary embryology. John Wiley & Sons., USA, pp. 221-223, 243-252. Available at: https://books.google.com.tr/books?id=lNYtDwAAQBAJ
Mcmurtry JP, Richards MP, Brocht DM, Schoen T, and Waldbillig R (1996). Developmental changes in serum insulin-like growth factor-I and insulinlike growth factor binding proteins in the turkey embryo. Poultry Science, 75(4): 563-569.
Mercola M and Stiles CD (1988). Growth factor superfamilies and mammalian embryogenesis. Development, 102(3): 451-460.
Neuhaus H and Hollemann T (2009). Kidney specific expression of cTPTE during development of the chick embryo. Gene Expression Patterns, 9(8): 568-571.
Owino V, Yang SY, and Goldspink G (2001). Age-related loss of skeletal muscle function and inability to express the autocrine form of insulin-like growth factor I (MGF) in response to mechanical overload. Federation of European Biochemical Societies Letters, 505(2): 259-263.
Ralphs JR, Wylie L, and Hill DJ (1990). Distribution of insulin-like growth factor peptides in the developing chick embryo. Development, 109(1): 51-58.
Robcis H, Caldes LT, and De Pablo F (1991). Insulin-like growth factor-I serum levels show a midembryogenesis peak in chicken that is absent in growth-retarded embryos cultured ex ovo. Endocrinology, 128(4): 1895-1901.
Saltan SK and Aslan Ş (2017). Immunohistochemical localization of ghrelin and IGF-I (insulin-like growth factor-I) in the liver and kidney tissues of melatonin-treated rats. Journal of Veterinary Science and Animal Husbandry, 5(4): 401.
Scanese CG and Dridi S (2021). Sturkie's avian physiology, 7th Edition. Elsevier., Amsterdam, Netherlands, pp. 413-425. Available at: https://shop.elsevier.com/books/sturkies-avian-physiology/scanes/978-0-12-819770-7
Schultz G, Khaw PT, Oxford K, Macauley S, Setten GV, and Chegini N (1994). Growth factors and ocular wound healing, Eye, 8(2): 184-187.
Shin D, Shin CH, Tucker J, Ober EA, Rentzsch F, Poss KD, Hammerschmidt Z, Mullins MC, and Stainier DY (2007). Bmp and Fgf signaling are essential for liver specification in zebrafish. Development, 134(11): 2041-2050.
Tașçı SK, Deprem T, Bingöl SA, and Akbulut Y (2018). The anatomical and histological structures of buzzard’s (Buteo buteo) small intestine and liver, and immunohistochemical localization of catalase, Kafkas University Faculty of Veterinary Medicine Journal, 24(1): 69-74.
Taşçı SK, Gülmez N, Aslan Ş, Deprem T, and Bingöl SA (2020). Immunohistochemical localization of catalase in geese (Anser anser) kidney. Kafkas University Faculty of Veterinary Medicine Journal, 26(1): 41-46.
Tekinarslan İİ, Unur E, Ülger H, Ekinci N, Ertekin T, Hacıalioğulları M, and Arslan S (2011). Effects of FGF-9 on embryonic development in vitro. Balkan Medical Journal, 28: 18-22.
Thompson AI, Conroy KP, and Henderson NC (2015). Hepatic stellate cells: Central modulators of hepatic carcinogenesis. BMC Gastroenterol, 15: 63.
Tilki M and Saatçi M (2013). Her yönüyle kaz yetiştiriciliği [Goose breeding in all its aspects]. Salmat Basım Yayıncılık, Ankara, pp. 91-94.
Uni Z, Yadgary L, and Yair R (2012). Nutritional limitations during poultry embryonic development. The Journal of Applied Poultry Research, 21(1): 175-184.
Webber EM, Wu JC, Wang L, Merlino G, and Fausto N (1994). Overexpression of transforming growth factor-alpha causes liver enlargement and increased hepatocyte proliferation in transgenic mice. The American Journal of Pathology, 145(2): 398-408.
Wolf HK, Zarnegar R, and Michalopoulos GK (1991). Localization of hepatocyte growth factor in human and rat tissues: An immunohistochemical study. Hepatology, 14(3): 488-494.
Yang L, Li LC, Lamaoqiezhong, Wang X, Wang WH, Wang YC, and Xu CR (2019). The contributions of mesoderm-derived cells in liver development. Seminars in Cell and Developmental Biology, 92: 63-76.
Yin C, Evason KJ, Asahina K, and Stainier DYR (2013). Hepatic stellate cells in liver development, regeneration, and cancer. The Journal of Clinical Investigation, 123(5): 1902-1910.
Yetkin G and Çelebi N (2001). Properties of transforming growth factor alpha, effects on cancer cells and ulcer wounds. FABAD Journal of Pharmaceutical Sciences, 26: 185-196.
Zaefarian F, Abdollahi MR, Cowieson A, and Ravindran V (2019). Avian Liver: The forgotten organ. Animals, 9(2): 63.
Zhang W, Yatskievych TA, Baker RK, and Antin PB (2004). Regulation of Hex gene expression and initial stages of avian hepatogenesis by Bmp and Fgf signaling. Developmental Biology, 268(2): 312-326.
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