. 2020 May 20;21(10):3606. doi: 10.3390/ijms21103606

Table 3.

Controversy about role of autophagy in influencing regeneration.

(a). Scientific Evidence that Activating Autophagy Is Promoting Liver Regeneration
Author Year	Research Model	Pathway	Autophagy Modulation	Parameters Indicating
Author Year	Research Model	Pathway	Autophagy Modulation	Enhanced Autophagy	Enhanced Regeneration	Reduced Autophagy	Reduced Regeneration
Takeo [13] 2014	Mice	Not investigated	Atg5-KO			LC3-II: --- p62: +++	BrdU: ---
Lin [26] 2015	C57BL/6 mice, Male	mTOR- independent	Amiodarone	LC3-II: +++ p62: ---	LBWR *: +++ Ki-67: +++
Lin [26] 2015	C57BL/6 mice, Male	mTOR- independent	Atg7-KD			LC3-II: ---	LBWR *: --- Ki-67: ---
Cheng [29] 2015	Liver progenitor cells	Not investigated	Overexpression of Beclin1	LC3-II: +++	PAS ^×: +++
Cheng [29] 2015	Liver progenitor cells	Not investigated	Beclin1-KD; Atg5-KD			LC3-II: --- p62: +++	CCK-8: --- PAS: ---
Liu [5] 2018	SD rats, Male, 3m, 22m; Primary rat hepatocytes	Not investigated	Young plasma	LC3-II: +++ p62: ---	Ki-67: +++
Liu [5] 2018	SD rats, Male, 3m, 22m; Primary rat hepatocytes	Not investigated	3-Methyladenine; Wortmannin			LC3-II: ---	Ki-67: ---
Jia [28] 2019	SD rats, Male, 5w	Not investigated	70% Portal Vein Ligation	LC3-II: +++	Cyclin D1: +++
Guha [164] 2019	Mice; MEFs; HEK293T cells.	IPMK-AMPK-ULK1; IPMK-AMPK-SIRT1	IPMK-KO			LC3-II: ---	Ki-67: --- Edu: ---
(b). Scientific Evidence that Inducing Autophagy Is Inhibiting Liver Regeneration
Author Year	Research Model	Pathway	Autophagy Modulation	Parameters Indicating
Author Year	Research Model	Pathway	Autophagy Modulation	Enhanced Autophagy	Reduced Regeneration	Reduced Autophagy	Enhanced Regeneration
Jiang [161] 2001	Harlan SD rats, Male	mTOR- dependent	Rapamycin	Not investigated	LWRR **: ---
Palme [159] 2008	Lewis rats, Male	mTOR- dependent	Rapamycin	Not investigated	Ki-67: ---
Fouraschen [160] 2013	C57BL/6 mice Male, 12–15w	mTOR- dependent	Rapamycin and Steroid dexamethasone	LC3-II: +++	BrdU: --- PCNA: --- LWRR **: ---
Kawaguchi [27] 2013	C57BL/6J mice, Male, 6–8w	mTOR- dependent	Temsirolimus	Not investigated	LBWR *: --- PCNA: ---
Shi [25] 2018	Balb/c mice, 6–8w	mTOR- dependent	Rapamycin	LC3-II: +++	LBWR *: --- PCNA: ---
			3-Methyladenine;			LC3-II: ---	LBWR *: +++ PCNA: +++
			ASPP2-haploinsufficient			LC3-II: --- p62: +++	LBWR *: +++ PCNA: +++

+++: Increase; ---: Decrease. * LBWR: Liver to body weight ratio. ** LWRR: Liver weight recovery rate. ^× used for estimating the capacity of LPCs differentiated into hepatocytes.